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Sample records for limb intracompartmental sepsis

  1. 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. ...

  2. 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, ...

  3. 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 ...

  4. 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 ...

  5. 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

  6. 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

  7. 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

  8. Intracompartmental pressure testing: results of an international survey of current clinical practice, highlighting the need for standardised protocols.

    PubMed

    Hislop, Matthew; Tierney, Paul

    2011-09-01

    Despite more recent non-invasive modalities generating some credence in the literature, intracompartmental pressure testing is still considered the 'gold standard' for investigating chronic exertional compartment syndrome (CECS). Intracompartmental pressure testing, when used correctly, has been shown to be accurate and reliable. However, it is a user-dependent investigation, and the manner in which the investigation is conducted plays a large role in the outcome of the test. Despite this, a standard, reproducible protocol for intracompartmental pressure testing has not been described. This results in confusion regarding interpretation of results and reduces the tests' reliability. A summary of the current understanding of CECS is presented, along with the results of a survey of specialists in Australia and New Zealand who perform intracompartmental pressure testing, which confirms that a uniform approach is currently not used in clinical practice. This highlights the need for a consensus and standardised approach to intracompartmental pressure testing. PMID:21900703

  9. Lower Leg Anterior and Lateral Intracompartmental Pressure Changes Before and After Classic Versus Skate Nordic Rollerskiing

    PubMed Central

    Woods, Katherine M.; Petron, David J.; Shultz, Barry B.; Hicks-Little, Charlie A.

    2015-01-01

    Context Chronic exertional compartment syndrome (CECS) is a debilitating condition resulting in loss of function and a decrease in athletic performance. Cases of CECS are increasing among Nordic skiers; therefore, analysis of intracompartmental pressures (ICPs) before and after Nordic skiing is warranted. Objective To determine if lower leg anterior and lateral ICPs and subjective lower leg pain levels increased after a 20-minute Nordic rollerskiing time trial and to examine if differences existed between postexercise ICPs for the 2 Nordic rollerskiing techniques, classic and skate. Design Crossover study. Setting Outdoor paved loop. Patients or Other Participants Seven healthy Division I Nordic skiers (3 men, 4 women; age = 22.71 ± 1.38 y, height = 175.36 ± 6.33 cm, mass = 70.71 ± 6.58 kg). Intervention(s) Participants completed two 20-minute rollerskiing time trials using the classic and skate technique in random order. The time trials were completed 7 days apart. Anterior and lateral ICPs and lower leg pain scores were obtained at baseline and at minutes 1 and 5 after rollerskiing. Main Outcome Measure(s) Anterior and lateral ICPs (mm Hg) were measured using a Stryker Quic STIC handheld monitor. Subjective measures of lower leg pain were recorded using the 11-point Numeric Rating Scale. Results Increases in both anterior (P = .000) and lateral compartment (P = .002) ICPs were observed, regardless of rollerskiing technique used. Subjective lower leg pain increased after the classic technique for the men from baseline to 1 minute postexercise and after the skate technique for the women. Significant 3-way interactions (technique × time × sex) were observed for the anterior (P = .002) and lateral (P = .009) compartment ICPs and lower leg pain (P = .005). Conclusions Postexercise anterior and lateral ICPs increased compared with preexercise ICPs after both classic and skate rollerskiing techniques. Lower leg pain is a primary symptom of CECS. The subjective

  10. 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 ...

  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. Acute Compartment Syndrome of the Limbs: Current Concepts and Management

    PubMed Central

    Mabvuure, Nigel Tapiwa; Malahias, Marco; Hindocha, Sandip; Khan, Wasim; Juma, Ali

    2012-01-01

    Acute compartment syndrome (ACS) of the limb refers to a constellation of symptoms, which occur following a rise in the pressure inside a limb muscle compartment. A failure or delay in recognising ACS almost invariably results in adverse outcomes for patients. Unrecognised ACS can leave patients with nonviable limbs requiring amputation and can also be life–threatening. Several clinical features indicate ACS. Where diagnosis is unclear there are several techniques for measuring intracompartmental pressure described in this review. As early diagnosis and fasciotomy are known to be the best determinants of good outcomes, it is important that surgeons are aware of the features that make this diagnosis likely. This clinical review discusses current knowledge on the relevant clinical anatomy, aetiology, pathophysiology, risk factors, clinical features, diagnostic procedures and management of an acute presentation of compartment syndrome. PMID:23248724

  13. 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 ...

  14. [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

  15. [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

  16. 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

  17. Artificial Limbs

    MedlinePlus

    ... you are missing an arm or leg, an artificial limb can sometimes replace it. The device, which ... activities such as walking, eating, or dressing. Some artificial limbs let you function nearly as well as ...

  18. Limb Loss

    MedlinePlus

    ... accidents and military combat Cancer Birth defects Some amputees have phantom pain, which is the feeling of ... problems, if you wear an artificial limb. Many amputees use an artificial limb. Learning how to use ...

  19. [Acute therapeutic measures for limb salvage Part 1 : Haemorrhage control, emergency revascularization, compartment syndrome].

    PubMed

    Willy, C; Stichling, M; Engelhardt, M; Vogt, D; Back, D A

    2016-05-01

    The primary care of Gustilo-Anderson type IIIC extremity injuries with relevant vessel lacerations is decisive for the success of a limb salvage procedure. This article shall present substantial emergency procedures for the salvage of the nutritive perfusion of a mangled extremity, based on the current literature. After provisory control of a peripheral haemorrhage (e. g. by manual pressure or tourniquet), an immediate decision must be made about the kind of emergency revascularization to be implemented as the limb salvage procedure. Here, the temporary intravascular shunt will be the fastest technique that can ensure a sufficient tissue perfusion in the case of vessel lacerations. Regarding the treatment of a fracture versus perfusion recovery, a shortening of ischemia time should have priority over fracture stabilization.If an acute compartment syndrome is suspected, a documented monitoring has to be performed in the limb salvage situation for 24 hours with clinical controls every 4 hours. Disproportional pain that does not respond to analgesics, and passive muscle stretching pain can be seen as cardinal symptoms. The positive predictive value of clinical findings is <15 %. During the observation period with an impending but not manifest compartment syndrome, an elevation of the extremity above heart level or its cooling are contraindicated. An intracompartmental pressure measurement is the most important instrument-based supplemental diagnostic method. The open fasciotomy of the affected compartments is the only causal therapy and should be performed as fast as possible. A decision against fasciotomy in cases of non-explicit clinical signs should not be made without a documented intracompartmental pressure measurement. PMID:27160729

  20. 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

  1. 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.

  2. The pathogenesis of sepsis.

    PubMed

    Bone, R C

    1991-09-15

    Sepsis and its sequelae (sepsis syndrome and septic shock) are increasingly common and are still potentially lethal diagnoses. Many mediators of the pathogenesis of sepsis have recently been described. These include tumor necrosis factor alpha (TNF alpha), interleukins, platelet activating factor, leukotrienes, thromboxane A2, and activators of the complement cascade. Neutrophil and platelet activation may also play a role. Other agents that may participate in the sepsis cascade include adhesion molecules, kinins, thrombin, myocardial depressant substance, beta-endorphin, and heat shock proteins. Endothelium-derived relaxing factor and endothelin-1 are released from the endothelium and seem to exert a regulatory effect, counterbalancing each other. A central mediator of sepsis does not seem to exist, although TNF alpha has been commonly proposed for this role. Animal studies are difficult to extrapolate to the clinical setting because of cross-species differences and variations in experimental design. Rather than being caused by any single pathogenic mechanism, it is more likely that sepsis is related to the state of activation of the target cell, the nearby presence of other mediators, and the ability of the target cell to release other mediators. Also important is the downregulation or negative feedback of these mediators or the generation of natural inflammation inhibitors, such as interleukin-4 and interleukin-8. Endothelial damage in sepsis probably results from persistent and repetitive inflammatory insults. Eventually, these insults produce sufficient damage that downregulation can no longer occur; this leads to a state of metabolic anarchy in which the body can no longer control its own inflammatory response. PMID:1872494

  3. 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

  4. 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

  5. Role of IL-15 in Sepsis-Induced Skeletal Muscle Atrophy and Proteolysis

    PubMed Central

    Cho, Hee-Young; Hah, Young-Sool

    2012-01-01

    Background Muscle wasting in sepsis is associated with increased proteolysis. Interleukin-15 (IL-15) has been characterized as an anabolic factor for skeletal muscles. Our study aims to investigate the role of IL-15 in sepsis-induced muscle atrophy and proteolysis. Methods Mice were rendered septic either by cecal ligation and puncture or by intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg i.p.). Expression of IL-15 mRNA and protein was determined by reverse transcriptase polymerase chain reaction and Western blot analysis in the control and septic limb muscles. C2C12 skeletal muscle cells were stimulated in vitro with either LPS or dexamethasone in the presence and absence of IL-15 and sampled at different time intervals (24, 48, or 72 hours). IL-15 (10µg/kg) was intraperitoneally administered 6 hours before sepsis induction and limb muscles were sampled after 24 hours of sepsis. Cathepsin L activity was determined to measure muscle proteolysis. Atrogin-1 and muscle-specific ring finger protein 1 (MuRF1) expressions in limb muscle protein lysates was analyzed. Results IL-15 mRNA expression was significantly lower in the limb muscles of septic mice compared to that of controls. Cathepsin L activity in C2C12 cells was significantly lower in presence of IL-15, when compared to that observed with individual treatments of LPS or dexamethasone or tumor necrosis factor α. Further, the limb muscles of mice pre-treated with IL-15 prior to sepsis induction showed a lower expression of atrogin-1 and MuRF1 than those not pre-treated. Conclusion IL-15 may play a role in protection against sepsis-induced muscle wasting; thereby, serving as a potential therapeutic target for sepsis-induced skeletal muscle wasting and proteolysis. PMID:23319993

  6. Sepsis Associated Encephalopathy

    PubMed Central

    Chaudhry, Neera; Duggal, Ashish Kumar

    2014-01-01

    Sepsis associated encephalopathy (SAE) is a common but poorly understood neurological complication of sepsis. It is characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection. The pathophysiology of SAE is complex and multifactorial including a number of intertwined mechanisms such as vascular damage, endothelial activation, breakdown of the blood brain barrier, altered brain signaling, brain inflammation, and apoptosis. Clinical presentation of SAE may range from mild symptoms such as malaise and concentration deficits to deep coma. The evaluation of cognitive dysfunction is made difficult by the absence of any specific investigations or biomarkers and the common use of sedation in critically ill patients. SAE thus remains diagnosis of exclusion which can only be made after ruling out other causes of altered mentation in a febrile, critically ill patient by appropriate investigations. In spite of high mortality rate, management of SAE is limited to treatment of the underlying infection and symptomatic treatment for delirium and seizures. It is important to be aware of this condition because SAE may present in early stages of sepsis, even before the diagnostic criteria for sepsis can be met. This review discusses the diagnostic approach to patients with SAE along with its epidemiology, pathophysiology, clinical presentation, and differential diagnosis. PMID:26556425

  7. Nutrition and sepsis.

    PubMed

    Cohen, Jonathan; Chin, w Dat N

    2013-01-01

    The effect of nutritional support in critically ill patients with sepsis has received much attention in recent years. However, many of the studies have produced conflicting results. As for all critically ill patients, nutritional support, preferably via the enteral route, should be commenced once initial resuscitation and adequate perfusion pressure is achieved. Where enteral feeding is impossible or not tolerated, parenteral nutrition (either as total or complimentary therapy) may safely be administered. Most positive studies relating to nutritional support and sepsis have been in the setting of sepsis prevention. Thus, the administration of standard nutrition formulas to critically ill patients within 24 h of injury or intensive care unit admission may decrease the incidence of pneumonia. Both arginine-supplemented enteral diets, given in the perioperative period, and glutamine-supplemented parenteral nutrition have been shown to decrease infections in surgical patients. Parenteral fish oil lipid emulsions as well as probiotics given in the perioperative period may also reduce infections in patients undergoing major abdominal operations, such as liver transplantation. There is little support at the present time for the positive effect of specific pharmaconutrients, in particular fish oil, probiotics, or antioxidants, in the setting of established sepsis. More studies are clearly required on larger numbers of more homogeneous groups of patients. PMID:23075593

  8. Revisiting caspases in sepsis

    PubMed Central

    Aziz, M; Jacob, A; Wang, P

    2014-01-01

    Sepsis is a life-threatening illness that occurs due to an abnormal host immune network which extends through the initial widespread and overwhelming inflammation, and culminates at the late stage of immunosupression. Recently, interest has been shifted toward therapies aimed at reversing the accompanying periods of immune suppression. Studies in experimental animals and critically ill patients have demonstrated that increased apoptosis of lymphoid organs and some parenchymal tissues contributes to this immune suppression, anergy and organ dysfunction. Immediate to the discoveries of the intracellular proteases, caspases for the induction of apoptosis and inflammation, and their striking roles in sepsis have been focused elaborately in a number of original and review articles. Here we revisited the different aspects of caspases in terms of apoptosis, pyroptosis, necroptosis and inflammation and focused their links in sepsis by reviewing several recent findings. In addition, we have documented striking perspectives which not only rewrite the pathophysiology, but also modernize our understanding for developing novel therapeutics against sepsis. PMID:25412304

  9. 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

  10. 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

  11. Neuroinflammation in sepsis: sepsis associated delirium.

    PubMed

    Piva, Simone; McCreadie, Victoria A; Latronico, Nicola

    2015-01-01

    Sepsis-associated delirium (SAD) is a clinical manifestation of the involvement of the central nervous system (CNS) during sepsis. The purpose of this review is to provide a concise overview of SAD including the epidemiology and current diagnostic criteria for SAD. We present in detail the pathophysiology with regards to blood-brain-barrier breakdown, cytokine activation and neurotransmitter deregulation. Treatment and prognosis for SAD are also briefly discussed. SAD is the most common form of delirium acquired in the ICU (Intensive Care Unit), and is described in about 50% of septic patients. Clinical features include altered level of consciousness, reduced attention, change in cognition and perceptual disturbances. Symptoms can reversible, but prolonged deficits can be observed in older patients. Pathophysiology of SAD is poorly understood, but involves microvascular, metabolic and, not least, inflammatory mechanisms leading to CNS dysfunction. These mechanisms can be different in SAD compared to ICU delirium associated with other conditions. SAD is diagnosed clinically using validated tools such as CAM-ICU (Confusion Assessment Method for the Intensive Care Medicine) or ICDSC (The Intensive Care Delirium Screening Checklist), which have good specificity but low sensitivity. Neuroimaging studies and EEG (Electroencephalography) can be useful complement to clinical evaluation to define the severity of the condition. Prompt diagnosis and eradication of septic foci whenever possible is vital. Preventive measures for SAD in the critically ill patient requiring long-term sedation include maintaining light levels of sedation using non-benzodiazepine sedatives (either propofol or dexmedetomidine). Early mobilization of patients in the ICU is also recommended. Antipsychotic drugs (haloperidol and atypical antipsychotics) are widely used to treat SAD, but firm evidence of their efficacy is lacking. PMID:25567339

  12. 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

  13. Complicated Perianal Sepsis.

    PubMed

    Mitra, Abhishek; Yadav, Amitabh; Mehta, Naimish; Varma, Vibha; Kumaran, Vinay; Nundy, Samiran

    2015-12-01

    Management of benign anorectal conditions like abscesses and haemorrhoids is usually uneventful. However, complicated perianal complications can result and have sparsely been reported in literature. Hereby, we report a series of seven patients who presented with rare sequelae like necrotising fasciitis, intraperitoneal or retroperitoneal involvement. All patients responded well to surgical management. Accordingly, complicated perianal sepsis warrants a timely and aggressive surgical intervention. PMID:27011454

  14. Sepsis-associated hyperlactatemia.

    PubMed

    Garcia-Alvarez, Mercedes; Marik, Paul; Bellomo, Rinaldo

    2014-01-01

    There is overwhelming evidence that sepsis and septic shock are associated with hyperlactatemia (sepsis-associated hyperlactatemia (SAHL)). SAHL is a strong independent predictor of mortality and its presence and progression are widely appreciated by clinicians to define a very high-risk population. Until recently, the dominant paradigm has been that SAHL is a marker of tissue hypoxia. Accordingly, SAHL has been interpreted to indicate the presence of an 'oxygen debt' or 'hypoperfusion', which leads to increased lactate generation via anaerobic glycolysis. In light of such interpretation of the meaning of SAHL, maneuvers to increase oxygen delivery have been proposed as its treatment. Moreover, lactate levels have been proposed as a method to evaluate the adequacy of resuscitation and the nature of the response to the initial treatment for sepsis. However, a large body of evidence has accumulated that strongly challenges such notions. Much evidence now supports the view that SAHL is not due only to tissue hypoxia or anaerobic glycolysis. Experimental and human studies all consistently support the view that SAHL is more logically explained by increased aerobic glycolysis secondary to activation of the stress response (adrenergic stimulation). More importantly, new evidence suggests that SAHL may actually serve to facilitate bioenergetic efficiency through an increase in lactate oxidation. In this sense, the characteristics of lactate production best fit the notion of an adaptive survival response that grows in intensity as disease severity increases. Clinicians need to be aware of these developments in our understanding of SAHL in order to approach patient management according to biological principles and to interpret lactate concentrations during sepsis resuscitation according to current best knowledge. PMID:25394679

  15. Cellular dysfunction in sepsis.

    PubMed

    Singer, Mervyn

    2008-12-01

    Cellular dysfunction is a commonplace sequelum of sepsis and other systemic inflammatory conditions. Impaired energy production (related to mitochondrial inhibition, damage, and reduced protein turnover) appears to be a core mechanism underlying the development of organ dysfunction. The reduction in energy availability appears to trigger a metabolic shutdown that impairs normal functioning of the cell. This may well represent an adaptive mechanism analogous to hibernation that prevents a massive degree of cell death and thus enables eventual recovery in survivors. PMID:18954700

  16. 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

  17. 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

  18. 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

  19. Maternal Sepsis and Septic Shock.

    PubMed

    Chebbo, Ahmad; Tan, Susanna; Kassis, Christelle; Tamura, Leslie; Carlson, Richard W

    2016-01-01

    The year 2015 marked the 200th anniversary of the birth of Ignaz Semmelweis, the Hungarian physician who identified unhygienic practices of physicians as a major cause of childbed fever or puerperal sepsis. Although such practices have largely disappeared as a factor in the development of chorioamnionitis and postpartum or puerperal endometritis, it is appropriate that this article on sepsis in pregnancy acknowledges his contributions to maternal health. This review describes the incidence and mortality of sepsis in pregnancy, methods to identify and define sepsis in this population, including scoring systems, causes, and sites of infection during pregnancy and parturition and management guidelines. PMID:26600449

  20. Surviving Sepsis: Taming a Deadly Immune Response

    MedlinePlus

    ... disclaimer . Subscribe Surviving Sepsis Taming a Deadly Immune Response Many people have never heard of sepsis, or ... tract infection) and then a powerful and harmful response by your body’s own immune system . “With sepsis, ...

  1. Alcoholic leukopenic pneumococcal sepsis.

    PubMed

    Alraiyes, Abdul Hamid; Shaheen, Khaldoon; Alraies, M Chadi

    2013-04-01

    Alcohol abuse has been associated with an increased mortality and morbidity due to increased aspiration, delirium tremens, and seizures. The association of pneumococcal lung infections and leukopenia in the setting of alcohol abuse are rarely reported; however, when present, severe lung infections can happen with severe lung injury and poor response to conventional therapy and ultimately, death. We are reporting a case of 55-year-old-man presented with shortness of breath, cough and altered mental status and eventually found with severe pneumococcal lung infection in the setting of leukopenia and long-term alcohol abuse representing alcoholic leukopenic pneumococcal sepsis syndrome. PMID:23930244

  2. Blood transfusion practices in sepsis

    PubMed Central

    Murthy, TVSP

    2014-01-01

    Sepsis is a clinical syndrome characterised by systemic inflammation due to infection. There is a spectrum with severity ranging from sepsis to severe sepsis and septic shock. Even with optimal treatment, mortality due to severe sepsis or septic shock is significant and poses a challenge to management. Antibiotics, source control, resuscitation with fluids, vasopressor and inotropic agents are the main-stay of treatment for septic shock. These may be supplemented with transfusion of red blood cells and or blood products, in the case of anaemia to sustain sufficient oxygen delivery[1] or to manage associated haematological issues. Transfusion in sepsis has always been a debatable issue, especially in relation to choice of the fluid and the role of blood or blood product transfusion. PMID:25535429

  3. [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

  4. Sepsis-induced purpura fulminans caused by Pasteurella multocida.

    PubMed

    Borges, Lisa; Oliveira, Nelson; Cássio, Isabel; Costa, Humberto

    2014-01-01

    A 52-year-old man was admitted with a cutaneous rash associated with septic shock and multiorganic failure, 6 days after a dog bite. He was started on empiric antibiotherapy and supportive measures. The patient's condition aggravated, with need for invasive mechanical ventilation and intermittent haemodialysis, and evolution from a petechiae-like rash to purpura and gangrene, culminating in bilateral lower limb amputation. The blood cultures revealed only Pasteurella multocida, after 10 days of incubation. P multocida infection is a rare cause of soft tissue infection that subsides with oral antibiotherapy. Infections causing sepsis are rare and appear in immunocompromised patients. Purpura fulminans induced by sepsis is a rare, life-threatening disorder. This syndrome should be recognised promptly, so early treatment is instituted. We found no case reports of purpura fulminans caused by Pasteurella infections in our literature review. PMID:24554680

  5. Sepsis-induced purpura fulminans caused by Pasteurella multocida

    PubMed Central

    Borges, Lisa; Oliveira, Nelson; Cássio, Isabel; Costa, Humberto

    2014-01-01

    A 52-year-old man was admitted with a cutaneous rash associated with septic shock and multiorganic failure, 6 days after a dog bite. He was started on empiric antibiotherapy and supportive measures. The patient's condition aggravated, with need for invasive mechanical ventilation and intermittent haemodialysis, and evolution from a petechiae-like rash to purpura and gangrene, culminating in bilateral lower limb amputation. The blood cultures revealed only Pasteurella multocida, after 10 days of incubation. P multocida infection is a rare cause of soft tissue infection that subsides with oral antibiotherapy. Infections causing sepsis are rare and appear in immunocompromised patients. Purpura fulminans induced by sepsis is a rare, life-threatening disorder. This syndrome should be recognised promptly, so early treatment is instituted. We found no case reports of purpura fulminans caused by Pasteurella infections in our literature review. PMID:24554680

  6. 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

  7. Antimicrobial Peptides in Human Sepsis

    PubMed Central

    Martin, Lukas; van Meegern, Anne; Doemming, Sabine; Schuerholz, Tobias

    2015-01-01

    Nearly 100 years ago, antimicrobial peptides (AMPs) were identified as an important part of innate immunity. They exist in species from bacteria to mammals and can be isolated in body fluids and on surfaces constitutively or induced by inflammation. Defensins have anti-bacterial effects against Gram-positive and Gram-negative bacteria as well as anti-viral and anti-yeast effects. Human neutrophil peptides (HNP) 1–3 and human beta-defensins (HBDs) 1–3 are some of the most important defensins in humans. Recent studies have demonstrated higher levels of HNP 1–3 and HBD-2 in sepsis. The bactericidal/permeability-increasing protein (BPI) attenuates local inflammatory response and decreases systemic toxicity of endotoxins. Moreover, BPI might reflect the severity of organ dysfunction in sepsis. Elevated plasma lactoferrin is detected in patients with organ failure. HNP 1–3, lactoferrin, BPI, and heparin-binding protein are increased in sepsis. Human lactoferrin peptide 1–11 (hLF 1–11) possesses antimicrobial activity and modulates inflammation. The recombinant form of lactoferrin [talactoferrin alpha (TLF)] has been shown to decrease mortality in critically ill patients. A phase II/III study with TLF in sepsis did not confirm this result. The growing number of multiresistant bacteria is an ongoing problem in sepsis therapy. Furthermore, antibiotics are known to promote the liberation of pro-inflammatory cell components and thus augment the severity of sepsis. Compared to antibiotics, AMPs kill bacteria but also neutralize pathogenic factors such as lipopolysaccharide. The obstacle to applying naturally occurring AMPs is their high nephro- and neurotoxicity. Therefore, the challenge is to develop peptides to treat septic patients effectively without causing harm. This overview focuses on natural and synthetic AMPs in human and experimental sepsis and their potential to provide significant improvements in the treatment of critically ill with severe infections

  8. Antimicrobial Peptides in Human Sepsis.

    PubMed

    Martin, Lukas; van Meegern, Anne; Doemming, Sabine; Schuerholz, Tobias

    2015-01-01

    Nearly 100 years ago, antimicrobial peptides (AMPs) were identified as an important part of innate immunity. They exist in species from bacteria to mammals and can be isolated in body fluids and on surfaces constitutively or induced by inflammation. Defensins have anti-bacterial effects against Gram-positive and Gram-negative bacteria as well as anti-viral and anti-yeast effects. Human neutrophil peptides (HNP) 1-3 and human beta-defensins (HBDs) 1-3 are some of the most important defensins in humans. Recent studies have demonstrated higher levels of HNP 1-3 and HBD-2 in sepsis. The bactericidal/permeability-increasing protein (BPI) attenuates local inflammatory response and decreases systemic toxicity of endotoxins. Moreover, BPI might reflect the severity of organ dysfunction in sepsis. Elevated plasma lactoferrin is detected in patients with organ failure. HNP 1-3, lactoferrin, BPI, and heparin-binding protein are increased in sepsis. Human lactoferrin peptide 1-11 (hLF 1-11) possesses antimicrobial activity and modulates inflammation. The recombinant form of lactoferrin [talactoferrin alpha (TLF)] has been shown to decrease mortality in critically ill patients. A phase II/III study with TLF in sepsis did not confirm this result. The growing number of multiresistant bacteria is an ongoing problem in sepsis therapy. Furthermore, antibiotics are known to promote the liberation of pro-inflammatory cell components and thus augment the severity of sepsis. Compared to antibiotics, AMPs kill bacteria but also neutralize pathogenic factors such as lipopolysaccharide. The obstacle to applying naturally occurring AMPs is their high nephro- and neurotoxicity. Therefore, the challenge is to develop peptides to treat septic patients effectively without causing harm. This overview focuses on natural and synthetic AMPs in human and experimental sepsis and their potential to provide significant improvements in the treatment of critically ill with severe infections. PMID

  9. Fast Action Can Prevent Sepsis Death: CDC

    MedlinePlus

    ... fullstory_160574.html Fast Action Can Prevent Sepsis Death: CDC Know the signs of extreme response to ... treated long before it causes severe illness or death, U.S. health officials report. Sepsis, or septicemia, occurs ...

  10. Sepsis caused by Flavimonas oryzihabitans.

    PubMed

    Lucas, K G; Kiehn, T E; Sobeck, K A; Armstrong, D; Brown, A E

    1994-07-01

    Previous reports of F. oryzihabitans sepsis involving central venous access devices reveal a relatively high rate of complications, including device removal, despite a course of broad-spectrum anti-microbials with compatible in vitro susceptibility results. In the present report of 22 cases of F. oryzihabitans sepsis treated at Memorial Sloan-Kettering Cancer Center from February 1986 through September 1993, the majority of CVAD-related infections with F. oryzihabitans were successfully treated with a 14-day course of antimicrobials with antipseudomonal activity, and removal of the device was usually not required. Factors that may complicate successful treatment of CVAD-related sepsis caused by F. oryzihabitans include polymicrobial infections and premature discontinuation of antibiotic therapy. PMID:8041243

  11. 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

  12. LIMB PROCESS DEVELOPMENT STUDIES

    EPA Science Inventory

    The report covers basic and applied studies concerned with three Limestone Injection Multistage Burner (LIMB) process objectives: (1) avoiding degradation of collection efficiency in the electrostatic precipitator (ESP) during LIMB, (2) achieving satisfactory sulfur dioxide (SO2)...

  13. Phantom limb pain

    MedlinePlus

    ... limb is still there. This is called phantom sensation. It may feel: Tingly Prickly Numb Hot or ... your missing limb is getting shorter (telescoping) These sensations slowly get weaker and weaker. You should also ...

  14. 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

  15. Scintigraphic evaluation in musculoskeletal sepsis

    SciTech Connect

    Merkel, K.D.; Fitzgerald, R.H. Jr.; Brown, M.L.

    1984-07-01

    In this article, the mechanism of technetium, gallium, and indium-labeled white blood cell localization in septic processes is detailed, and the method of interpretation of these three isotopes with relationship to musculoskeletal infection is outlined. Specific clinical application of technetium, gallium, and indium-labeled white blood cell imaging for musculoskeletal sepsis is reviewed.

  16. 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

  17. New approaches to the study of sepsis

    PubMed Central

    Ward, Peter A

    2012-01-01

    Models of sepsis have been instructive in understanding the sequence of events in animals and, to an extent, in humans with sepsis. Events developing early in sepsis suggest that a hyperinflammatory state exists, accompanied by a buildup of oxidants in tissues reflective of a redox imbalance. Development of immunosuppression and degraded innate and adaptive immune responses are well-established complications of sepsis. In addition, there is robust activation of the complement system, which contributes to the harmful effects of sepsis. These events appear to be associated with development of multiorgan failure. The relevance of animal models of sepsis to human sepsis and the failure of human clinical trials are discussed, together with suggestions as to how clinical trial design might be improved. PMID:23208733

  18. Congenital limb deficiency disorders.

    PubMed

    Wilcox, William R; Coulter, Colleen P; Schmitz, Michael L

    2015-06-01

    Congenital limb deficiency disorders (LDDs) are birth defects characterized by the aplasia or hypoplasia of bones of the limbs. Limb deficiencies are classified as transverse, those due to intrauterine disruptions of previously normal limbs, or longitudinal, those that are isolated or associated with certain syndromes as well as chromosomal anomalies. Consultation with a medical geneticist is advisable. Long-term care should occur in a specialized limb deficiency center with expertise in orthopedics, prosthetics, and occupational and physical therapy and provide emotional support and contact with other families. With appropriate care, most children with LDDs can lead productive lives. PMID:26042905

  19. PIRO concept: Staging of sepsis

    PubMed Central

    Rathour, S; Kumar, S; Hadda, V; Bhalla, A; Sharma, N; Varma, S

    2015-01-01

    Introduction: Sepsis is common presenting illness to the emergency services and one of the leading causes of hospital mortality. Researchers and clinicians have realized that the systemic inflammatory response syndrome concept for defining sepsis is less useful and lacks specificity. The predisposition, infection (or insult), response and organ dysfunction (PIRO) staging of sepsis similar to malignant diseases (TNM staging) might give better information. Materials and Methods: A prospective observational study was conducted in emergency medical services attached to medicine department of a tertiary care hospital in Northern India. Patients with age 18 years or more with proven sepsis were included in the first 24 hours of the diagnosis. Two hundred patients were recruited. Multivariate logistic regression analysis was done to assess the factors that predicted in-hospital mortality. Results: Two hundred patients with proven sepsis, admitted to the emergency medical services were analysed. Male preponderance was noted (M: F ratio = 1.6:1). Mean age of study cohort was 50.50 ± 16.30 years. Out of 200 patients, 116 (58%) had in-hospital mortality. In multivariate logistic regression analysis, the factors independently associated with in-hospital mortality for predisposition component of PIRO staging were age >70 years, chronic obstructive pulmonary disease, chronic liver disease, cancer and presence of foley's catheter; for infection/insult were pneumonia, urinary tract infection and meningitis/encephalitis; for response variable were tachypnea (respiratory rate >20/minute) and bandemia (band >5%). Organ dysfunction variables associated with hospital mortality were systolic blood pressure <90mm Hg, prolonged activated partial thromboplastin time, raised serum creatinine, partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) ratio <300, decreased urine output in first two hours of emergency presentation and Glasgow coma scale ≤9. Each

  20. Diagnosing sepsis - The role of laboratory medicine.

    PubMed

    Fan, Shu-Ling; Miller, Nancy S; Lee, John; Remick, Daniel G

    2016-09-01

    Sepsis is the host response to microbial pathogens resulting in significant morbidity and mortality. An accurate and timely diagnosis of sepsis allows prompt and appropriate treatment. This review discusses laboratory testing for sepsis because differentiating systemic inflammation from infection is challenging. Procalcitonin (PCT) is currently an FDA approved test to aid in the diagnosis of sepsis but with questionable efficacy. However, studies support the use of PCT for antibiotic de-escalation. Serial lactate measurements have been recommended for monitoring treatment efficacy as part of sepsis bundles. The 2016 sepsis consensus definitions include lactate concentrations >2mmol/L (>18mg/dL) as part of the definition of septic shock. Also included in the 2016 definitions are measuring bilirubin and creatinine to determine progression of organ failure indicating worse prognosis. Hematologic parameters, including a simple white blood cell count and differential, are frequently part of the initial sepsis diagnostic protocols. Several new biomarkers have been proposed to diagnose sepsis or to predict mortality, but they currently lack sufficient sensitivity and specificity to be considered as stand-alone testing. If sepsis is suspected, new technologies and microbiologic assays allow rapid and specific identification of pathogens. In 2016 there is no single laboratory test that accurately diagnoses sepsis. PMID:27387712

  1. 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

  2. Biosensor of endotoxin and sepsis

    NASA Astrophysics Data System (ADS)

    Shao, Yang; Wang, Xiang; Wu, Xi; Gao, Wei; He, Qing-hua; Cai, Shaoxi

    2001-09-01

    To investigate the relation between biosensor of endotoxin and endotoxin of plasma in sepsis. Method: biosensor of endotoxin was designed with technology of quartz crystal microbalance bioaffinity sensor ligand of endotoxin were immobilized by protein A conjugate. When a sample soliton of plasma containing endotoxin 0.01, 0.03, 0.06, 0.1, 0.5, 1.0Eu, treated with perchloric acid and injected into slot of quartz crystal surface respectively, the ligand was released from the surface of quartz crystal to form a more stable complex with endotoxin in solution. The endotoxin concentration corresponded to the weight change on the crystal surface, and caused change of frequency that occurred when desorbed. The result was biosensor of endotoxin might detect endotoxin of plasma in sepsis, measurements range between 0.05Eu and 0.5Eu in the stop flow mode, measurement range between 0.1Eu and 1Eu in the flow mode. The sensor of endotoxin could detect the endotoxin of plasm rapidly, and use for detection sepsis in clinically.

  3. Early-Onset Neonatal Sepsis

    PubMed Central

    Simonsen, Kari A.; Anderson-Berry, Ann L.; Delair, Shirley F.

    2014-01-01

    SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS. PMID:24396135

  4. The molecular pathogenesis of cholestasis in sepsis

    PubMed Central

    Bhogal, Harjit K.; Sanyal, Arun J.

    2016-01-01

    Sepsis-induced cholestasis is a complication of infection. Infections cause systemic and intrahepatic increase in proinflammatory cytokines which result in impaired bile flow ie. cholestasis. Several other mediators of impairment in bile flow have been identified under conditions of sepsis such as increased nitric oxide production and decreased aquaporin channels. The development of cholestasis may also further worsen inflammation. The molecular basis of normal bile flow and mechanisms of impairment in sepsis are discussed. PMID:23276972

  5. Autophagy in sepsis: Degradation into exhaustion?

    PubMed

    Ho, Jeffery; Yu, Jun; Wong, Sunny H; Zhang, Lin; Liu, Xiaodong; Wong, Wai T; Leung, Czarina C H; Choi, Gordon; Wang, Maggie H T; Gin, Tony; Chan, Matthew T V; Wu, William K K

    2016-07-01

    Autophagy is one of the innate immune defense mechanisms against microbial challenges. Previous in vitro and in vivo models of sepsis demonstrated that autophagy was activated initially in sepsis, followed by a subsequent phase of impairment. Autophagy modulation appears to be protective against multiple organ injuries in these murine sepsis models. This is achieved in part by preventing apoptosis, maintaining a balance between the productions of pro- and anti-inflammatory cytokines, and preserving mitochondrial functions. This article aims to discuss the role of autophagy in sepsis and the therapeutic potential of autophagy enhancers. PMID:27172163

  6. 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

  7. Sepsis management in the deployed field hospital.

    PubMed

    Johnston, Andrew McD; Easby, D; Ewington, I

    2013-09-01

    Sepsis, a syndrome caused by severe infection, affects a small proportion of military casualties but has a significant effect in increasing morbidity and mortality, including causing some preventable deaths. Casualties with abdominal trauma and those with significant tissue loss appear to be at a greater risk of sepsis. In this article, the diagnosis and management of sepsis in military casualties with reference to the Surviving Sepsis Campaign guidelines are examined. We discuss the management considerations specific to military casualties in the deployed setting and also discuss factors affecting evacuation by the UK Royal Air Force Critical Care Air Support Team. PMID:24109139

  8. Systems for Paediatric Sepsis: A Global Survey

    PubMed Central

    Kang, KT; Chandler, HK; Espinosa, V; Kissoon, N

    2014-01-01

    ABSTRACT Objectives: To evaluate the resources available for early diagnosis and treatment of paediatric sepsis at hospitals in developing and developed countries. Methods: This was a voluntary online survey involving 101 hospitals from 41 countries solicited through the World Federation of Pediatric Intensive and Critical Care Societies contact list and website. The survey was designed to assess the spectrum of sepsis epidemiology, patterns of applied therapies, availability of resources and barriers to optimal sepsis treatment. Results: Ninety per cent of respondents represented a tertiary or general hospital with paediatric intensive care facilities, including 63% from developed countries. Adequate triage services were absent in more than 20% of centres. Insufficiently trained personnel and lack of a sepsis protocol was reported in 40% of all sites. While there were specific guidelines for sepsis management in 78% of centres (n = 100), protocols for assessing sepsis patients were not applied in nearly 70% of centres. Lack of parental recognition of sepsis and failure of referring centres to diagnose sepsis were identified as major barriers by more than 50% of respondents. Conclusions: Even among centres with no significant resource constraints and advanced medical systems, significant deficits in sepsis care exist. Early recognition and management remains a key issue and may be addressed through improved triage, augmented support for referring centres and public awareness. Focussed research is necessary at the institutional level to identify and address specific barriers. PMID:25867557

  9. Development and Implementation of Sepsis Alert Systems.

    PubMed

    Harrison, Andrew M; Gajic, Ognjen; Pickering, Brian W; Herasevich, Vitaly

    2016-06-01

    Development and implementation of sepsis alert systems is challenging, particularly outside the monitored intensive care unit (ICU) setting. Barriers to wider use of sepsis alerts include evolving clinical definitions of sepsis, information overload, and alert fatigue, due to suboptimal alert performance. Outside the ICU, barriers include differences in health care delivery models, charting behaviors, and availability of electronic data. Current evidence does not support routine use of sepsis alert systems in clinical practice. Continuous improvement in the afferent and efferent aspects will help translate theoretic advantages into measurable patient benefit. PMID:27229639

  10. [Disturbances of hemostasis in sepsis].

    PubMed

    Novotný, J; Penka, M

    2012-06-01

    Immune system and hemostasis are closely bound together. When one of these systems is activated, another is set in motion too. This is especially noticeable in polytraumas, inflammation, shocks etc. The most important activator of immune system and hemostasis is sepsis. In sepsis there is a vigorous stimulation of immune response because of a liberation of a lot of cytokines and proinflammatory molecules. This may lead to an extrem picture of systemic inflammatory response syndrome. In systemic inflammatory response syndrome a downregulation of thrombomodulin and endothelial protein C receptor on the surface of intact endothel may be detected and there is an upregulation of release of the tissue-type plasminogen activator with a switch to plasminogen activator inhibitor 1 release. There is lowering of activated protein C and fibrinolytic activation followed by fibrinolytic inhibition in septic patients. Consequently we can see consumption of coagulation factors, inhibitors (antithrombin, protein C, and tissue factor pathway inhibitor), microangiopatic hemolysis and thrombocytopenia with a picture of disseminated intravascular coagulation in these patients. The diagnosis of disseminated intravascular coagulation is not uniforme in the literature. Expression of tissue factor on monocytes and endothelium may aggravate this "circulus vitiosus" with serious microcirculatory failure in sense of MOF/MODS (mutliorgan failure/multiorgan dysfunction syndrome). The first steps in the therapy of sepsis represent the treatment of cause of sepsis, vigorous hydratation and maintenance of circulation and pulmonary function, glycemic control etc, the prevention and blocking of the undesirable activation of hemostasis and inflammation being equally important. The treatment with minidoses of heparin was implemented in the past and the question, if this therapy is indicated is not answered yet. The clinical studies of the suitability of the treatment with natural inhibitors of

  11. 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

  12. 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

  13. Improving the Odds of Surviving Sepsis

    MedlinePlus

    ... Improving the Odds of Surviving Sepsis Inside Life Science View All Articles | Inside Life Science Home Page Improving the Odds of Surviving Sepsis ... Threatening Bacterial Infection Remains Mysterious This Inside Life Science article also appears on LiveScience . Learn about related ...

  14. Cytokine profile in elderly patients with sepsis

    PubMed Central

    Kumar, Anil T.; Sudhir, U.; Punith, K.; Kumar, Rahul; Ravi Kumar, V. N.; Rao, Medha Y.

    2009-01-01

    Context: Sepsis is a serious health problem in the elderly with a high degree of mortality. There is very limited data available in elderly subjects regarding the markers for sepsis. Development of good markers will help in overall management and prediction of sepsis. Objectives: Serial estimation of Interleukin-6 (IL-6) and Tumor Necrosis Factor-Alpha (TNF-α) and their correlation with mortality in sepsis in elderly patients and to determine the influence of gender on cytokine production and mortality in elderly patients with sepsis. Settings and Design: The prospective study was conducted at our tertiary care center from April 2007 to September 2008. Elderly Patients satisfying the Systemic Inflammatory Response Syndrome (SIRS) criteria were included. Methods and Material: TNF-α and IL-6 were estimated in 30 elderly patients admitted to our intensive care unit with SIRS and sepsis. The estimations were done on day 1, 3 and 7 of admission. Statistical Analysis Used: Student and paired ‘t’ tests, and ANOVA, which were further followed up by post-hoc ‘t’ tests with Bonferroni correction using SPSS. Results: Reducing levels of IL-6 levels from day 1 to 7 was found in the survivor group. TNF-α level was significantly low on day 1 in the nonsurvivor female group. Conclusions: Serial estimation of cytokines in elderly patients with sepsis will help in prediction of mortality. Female gender was an independent predictor of increased morality in critically ill patients with sepsis. PMID:19881187

  15. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1989-06-15

    The basic goal of the Limestone Injection Multistage Burner (LIMB) demonstration is to extend LIMB technology development to a full- scale application on a representative wall-fired utility boiler. The successful retrofit of LIMB to an existing boiler is expected to demonstrate that (a) reductions of 50 percent or greater in SO{sub x} and NO{sub x} emissions can be achieved at a fraction of the cost of add-on FGD systems, (b) boiler reliability, operability, and steam production can be maintained at levels existing prior to LIMB retrofit, and (c) technical difficulties attributable to LIMB operation, such as additional slagging and fouling, changes in ash disposal requirements, and an increased particulate load, can be resolved in a cost-effective manner. The primary fuel to be used will be an Ohio bituminous coal having a nominal sulfur content of 3 percent or greater.

  16. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1989-11-15

    The basic goal of the Limestone Injection Mitigation Burner (LIMB) demonstration is to extend LIMB technology development to a full- scale application on a representative wall-fired utility boiler. The successful retrofit of LIMB to an existing boiler is expected to demonstrate that (a) reductions of 50 percent or greater in SO{sub x} and NO{sub x} emissions can be achieved at a fraction of the cost of add-on FGD systems, (b) boiler reliability, operability, and steam production can be maintained at levels existing prior to LIMB retrofit, and (c) technical difficulties attributable to LIMB operation, such as additional slagging and fouling, changes in ash disposal requirements, and an increased particulate load, can be resolved in a cost-effective manner. The primary fuel to be used will be an Ohio bituminous coal having a nominal sulfur content of 3 percent or greater.

  17. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1989-03-15

    The basic goal of the Limestone Injection Multistage Burner (LIMB) demonstration is to extend LIMB technology development to a full- scale application on a representative wall-fired utility boiler. The successful retrofit of LIMB to an existing boiler is expected to demonstrate that (a) reductions of 50 percent or greater in SO{sub x} and NO{sub x} emissions can be achieved at a fraction of the cost of add-on FGD systems, (b) boiler reliability, operability, and steam production can be maintained at levels existing prior to LIMB retrofit, and (c) technical difficulties attributable to LIMB operation, such as additional slagging and fouling, changes in ash disposal requirements, and an increased particulate load, can be resolved in a cost-effective manner. The primary fuel to be used will be an Ohio bituminous coal having a nominal sulfur content of 3 percent or greater.

  18. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1988-12-15

    The basic goal of the Limestone Injection Multistage Burner (LIMB) demonstration is to extend LIMB technology development to a full- scale application on a representative wall-fired utility boiler. The successful retrofit of LIMB to an existing boiler is expected to demonstrate that (a) reductions of 50 percent or greater in SO{sub x} and NO{sub x} emissions can be achieved at a fraction of the cost of add-on FGD systems, (b) boiler reliability, operability, and steam production can be maintained at levels existing prior to LIMB retrofit, and (c) technical difficulties attributable to LIMB operation, such as additional slagging and fouling, changes in ash disposal requirements, and an increased particulate load, can be resolved in a cost-effective manner. The primary fuel to be used will be an Ohio bituminous coal having a nominal sulfur content of 3 percent or greater.

  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. LIMB demonstration project extension

    SciTech Connect

    Not Available

    1990-09-21

    The purpose of the DOE limestone injection multistage burner (LIMB) Demonstration Project Extension is to extend the data base on LIMB technology and to expand DOE's list of Clean Coal Technologies by demonstrating the Coolside process as part of the project. The main objectives of this project are: to demonstrate the general applicability of LIMB technology by testing 3 coals and 4 sorbents (total of 12 coal/sorbent combinations) at the Ohio Edison Edgewater plant; and to demonstrate that Coolside is a viable technology for improving precipitator performance and reducing sulfur dioxide emissions while acceptable operability is maintained. Progress is reported. 3 figs.

  1. Out on a Limb: Investigating the Anatomy of Tree Limbs

    ERIC Educational Resources Information Center

    Shaw, Edward L.

    2008-01-01

    The author presents several upper elementary science activities involving tree limbs that were collected after severe weather conditions. The activities involved 3rd-grade students arranging tree limb pieces in the correct order from the trunk to the tip of the limb, measuring the pieces, determining the age of a tree limb by its rings,…

  2. Sepsis

    MedlinePlus

    ... 100.4°F [38°C] and above rectal temperature) in newborns and young infants labored or unusual breathing change in skin color (paler than usual or mildly bluish) or a rash listlessness or lethargy change in the sound of the baby's cry or excessive crying change ...

  3. 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

  4. 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

  5. Antithrombotic Agents in the Management of Sepsis.

    PubMed

    Iqbal, Omer; Tobu, Mahmut; Hoppenstead, Debra; Aziz, Salim; Messmore, Harry; Fareed, Jawed

    2002-09-01

    Sepsis, a systemic inflammatory syndrome, is a response to infection and when associated with multiple organ dysfunction is termed, severe sepsis. It remains a leading cause of mortality in the critically ill. The response to the invading bacteria may be considered as a balance between proinflammatory and antiinflammatory reaction. While an inadequate proinflammatory reaction and a strong antiinflammatory response could lead to overwhelming infection and death of the patient, a strong and uncontrolled proinflammatory response, manifested by the release of proinflammatory mediators may lead to microvascular thrombosis and multiple organ failure. Endotoxin triggers sepsis by releasing various mediators including tumor necrosis factor-alpha and interleukin-1(IL-1). These cytokines activate the complement and coagulation systems, release adhesion molecules, prostaglandins, leukotrienes, reactive oxygen species and nitric oxide (NO). Other mediators involved in the sepsis syndrome include IL-1, IL-6 and IL-8; arachidonic acid metabolites; platelet activating factor (PAF); histamine; bradykinin; angiotensin; complement components and vasoactive intestinal peptide. These proinflammatory responses are counteracted by IL-10. Most of the trials targeting the different mediators of proinflammatory response have failed due a lack of correct definition of sepsis. Understanding the exact pathophysiology of the disease will enable better treatment options. Targeting the coagulation system with various anticoagulant agents including antithrombin, activated protein C (APC), tissue factor pathway inhibitor (TFPI) is a rational approach. Many clinical trials have been conducted to evaluate these agents in severe sepsis. While trials on antithrombin and TFPI were not so successful, the double-blind, placebo-controlled, phase III trial of recombinant human activated protein C worldwide evaluation in severe sepsis (PROWESS) was successful, significantly decreasing mortality when

  6. [Phantom limb pains].

    PubMed

    Giraux, Pascal

    2015-03-01

    With the radical experience of an amputation, the adaptation of body image is often incomplete. Some people experience phantom body perceptions, often painful and difficult to treat, after the amputation of a limb. PMID:26145132

  7. Dysglycemia and Glucose Control During Sepsis.

    PubMed

    Plummer, Mark P; Deane, Adam M

    2016-06-01

    Sepsis predisposes to disordered metabolism and dysglycemia; the latter is a broad term that includes hyperglycemia, hypoglycemia, and glycemic variability. Dysglycemia is a marker of illness severity. Large randomized controlled trials have provided considerable insight into the optimal blood glucose targets for critically ill patients with sepsis. However, it may be that the pathophysiologic consequences of dysglycemia are dynamic throughout the course of a septic insult and also altered by premorbid glycemia. This review highlights the relevance of hyperglycemia, hypoglycemia, and glycemic variability in patients with sepsis with an emphasis on a rational approach to management. PMID:27229647

  8. Sepsis Resuscitation: Fluid Choice and Dose.

    PubMed

    Semler, Matthew W; Rice, Todd W

    2016-06-01

    Sepsis is a common and life-threatening inflammatory response to severe infection treated with antibiotics and fluid resuscitation. Despite the central role of intravenous fluid in sepsis management, fundamental questions regarding which fluid and in what amount remain unanswered. Recent advances in understanding the physiologic response to fluid administration, and large clinical studies examining resuscitation strategies, fluid balance after resuscitation, colloid versus crystalloid solutions, and high- versus low-chloride crystalloids, inform the current approach to sepsis fluid management and suggest areas for future research. PMID:27229641

  9. Revascularization Surgery: Its Efficacy for Limb Salvage in Diabetic Foot.

    PubMed

    Chang, Tzu-Yen; Shieh, Shyh-Jou

    2016-03-01

    The estimated prevalence of diabetes is 9.78% in Taiwan. The lifetime risk for patients with diabetes to have foot ulcers might be as high as 25%. About 15% of these patients require major limb amputation because of ischemia and infection. Peripheral artery disease is still a major problem involved in diabetic foot disease and the cause for major amputation despite an increase in the prevalence of revascularization surgery and new revascularization techniques over the past 20 years. We investigated the major limb amputation rates in patients with diabetic foot and critical limb ischemia who had undergone revascularization surgery in our hospital. The records of 42 patients who had undergone revascularization surgery for diabetic foot were retrospectively reviewed. Nineteen patients (45%) required major limb amputation despite revascularization. The affected limbs of only 15 patients (36%) were salvaged. Four patients died soon after surgery because of comorbidities, and another 4 were lost to follow-up. Two patients died from procedure-related sepsis, and overall perioperative mortality was 4.8%. Ten predictive risk factors (duration of diabetes, history of smoking, coronary artery disease, congestive heart failure, cerebral vascular accident, contralateral amputation, end-stage renal disease, fever episode, wound infection severity score, and arterial obstruction level) were included for analysis. Although none was significant, long-duration diabetes (OR: 1.13), end-stage renal disease (OR: 10.02), wound infection (OR: 1.56), and infrapopliteal lesions (OR: 3.00) tended to be unfavorable predictive risk factors of limb amputation. Revascularization surgery is still potentially beneficial for these patients-eg, it decreases the contralateral limb amputation rate by 7.5%-if done early in high-risk patients. PMID:26808765

  10. Sepsis, venous return, and teleology.

    PubMed

    McNeilly, R G

    2014-11-01

    An understanding of heart-circulation interaction is crucial to our ability to guide our patients through an episode of septic shock. Our knowledge has advanced greatly in the last one hundred years. There are, however, certain empirical phenomena that may lead us to question the wisdom of our prevailing treatment algorithm. Three extreme but iatrogenically possible haemodynamic states exist. Firstly, inappropriately low venous return; secondly, overzealous arteriolar constriction; and finally, misguided inotropy and chronotropy. Following an unsuccessful fluid challenge, it would be logical to first set the venous tone, then set the cardiac rate and contractility, and finally set the peripheral vascular resistance. It is hypothesized that a combination of dihydroergotamine, milrinone and esmolol should be superior to a combination of noradrenaline and dobutamine for surviving sepsis. PMID:25245463

  11. Sepsis after autologous fat grafting.

    PubMed

    Talbot, Simon G; Parrett, Brian M; Yaremchuk, Michael J

    2010-10-01

    Autologous fat grafting is an increasingly popular technique, with numerous examples of excellent results. Adherence to key principles, including sterile technique and low-volume injection throughout layers of tissue, appears to be critical to obtaining good results. Reports of adverse outcomes are infrequent, but several case reports document both infectious and aesthetic complications. This case report represents an extreme complication, including abscess formation, life-threatening sepsis, and residual deformity. It serves as yet another reminder that early adoption of surgical procedures by those without a sound understanding of the underlying principles and techniques can have disastrous consequences. Furthermore, physicians operating on any patient must understand the potential for complications and be able to manage these appropriately when they occur. PMID:20885205

  12. Xenopus Limb bud morphogenesis.

    PubMed

    Keenan, Samuel R; Beck, Caroline W

    2016-03-01

    Xenopus laevis, the South African clawed frog, is a well-established model organism for the study of developmental biology and regeneration due to its many advantages for both classical and molecular studies of patterning and morphogenesis. While contemporary studies of limb development tend to focus on models developed from the study of chicken and mouse embryos, there are also many classical studies of limb development in frogs. These include both fate and specification maps, that, due to their age, are perhaps not as widely known or cited as they should be. This has led to some inevitable misinterpretations- for example, it is often said that Xenopus limb buds have no apical ectodermal ridge, a morphological signalling centre located at the distal dorsal/ventral epithelial boundary and known to regulate limb bud outgrowth. These studies are valuable both from an evolutionary perspective, because amphibians diverged early from the amniote lineage, and from a developmental perspective, as amphibian limbs are capable of regeneration. Here, we describe Xenopus limb morphogenesis with reference to both classical and molecular studies, to create a clearer picture of what we know, and what is still mysterious, about this process. PMID:26404044

  13. A prospective treatment for sepsis.

    PubMed

    Shahidi Bonjar, Mohammad Rashid; Shahidi Bonjar, Leyla

    2015-01-01

    The present paper proposes a prospective auxiliary treatment for sepsis. There exists no record in the published media on the subject. As an auxiliary therapy, efficacious extracorporeal removal of sepsis-causing bacterial antigens and their toxins (BATs) from the blood of septic patients is discussed. The principal component to this approach is a bacterial polyvalent antibody-column (BPVAC), which selectively traps wide spectrum of BATs from blood in an extracorporeal circuit, and detoxified blood returns back to the patient's body. BPVAC treatment would be a device of targeted medicine. Detoxification is performed under supervision of trained personnel using simple blood-circulating machines in which blood circulates from the patient to BPVAC and back to the patient aseptically. BPVACs' reactive sites consist of carbon nanotubes on which a vast spectra of polyvalent BATs-antibodies are bond to. The devise acts as a biological filter that selectively immobilizes harmful BATs from intoxicated blood; however, no dialysis is involved. For effective neutralization, BPVAC provides large contact surface area with blood. BPVAC approach would have advantages of: 1) urgent neutralization of notorious BATs from blood of septic patients; 2) applicability in parallel with conventional treatments; 3) potential to minimize side effects of the malady; 4) applicability for a vast range of BATs; 5) potential to eliminate contact of BATs with internal tissues and organs; 6) tolerability by patients sensitive to antiserum injections; 7) capability for universal application; 8) affectivity when antibiotic-resistant bacteria are involved and the physician has no or limited access to appropriate antibiotics; and 10) being a single-use, disposable, and stand-alone device. Before using it for clinical trials in human beings, it should pass animal evaluations accurately; however, research works should optimize its implementation in human beings. For optimization, it needs appropriate

  14. 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

  15. 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

  16. Sepsis in Pregnancy: Identification and Management.

    PubMed

    Albright, Catherine M; Mehta, Niharika D; Rouse, Dwight J; Hughes, Brenna L

    2016-01-01

    Sepsis accounts for up to 28% of all maternal deaths. Prompt, appropriate treatment improves maternal and fetal morbidity and mortality. To date, there are no validated tools for identification of sepsis in pregnant women, and tools used in the general population tend to overestimate mortality. Once identified, management of pregnancy-associated sepsis is goal-directed, but because of the lack of studies of sepsis management in pregnancy, it must be assumed that modifications need to be made on the basis of the physiologic changes of pregnancy. Key to management is early fluid resuscitation and early initiation of appropriate antimicrobial therapy directed toward the likely source of infection or, if the source is unknown, empiric broad-spectrum therapy. Efforts directed at identifying the source of infection and appropriate source control measures are critical. Development of an illness severity scoring system and treatment algorithms validated in pregnant women needs to be a research priority. PMID:26825620

  17. 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

  18. Case of Sepsis Caused by Bifidobacterium longum

    PubMed Central

    Ha, Gyoung Yim; Yang, Chang Heon; Kim, Heesoo; Chong, Yunsop

    1999-01-01

    We report a case of sepsis caused by Bifidobacterium longum in a 19-year-old male who had developed high fever, jaundice, and hepatomegaly after acupuncture therapy with small gold needles. Anaerobic, non-spore-forming, gram-positive bacilli were isolated from his blood and finally identified as B. longum. He recovered completely after treatment with ticarcillin and metronidazole. To our knowledge, this is the first report of incidental sepsis caused by B. longum. PMID:10074561

  19. 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

  20. Necrotising soft-tissue infections of the upper limb: risk factors for amputation and death.

    PubMed

    Uehara, K; Yasunaga, H; Morizaki, Y; Horiguchi, H; Fushimi, K; Tanaka, S

    2014-11-01

    Necrotising soft-tissue infections (NSTIs) of the upper limb are uncommon, but potentially life-threatening. We used a national database to investigate the risk factors for amputation of the limb and death. We extracted data from the Japanese Diagnosis Procedure Combination database on 116 patients (79 men and 37 women) who had a NSTI of the upper extremity between 2007 and 2010. The overall in-hospital mortality was 15.5%. Univariate analysis of in-hospital mortality showed that the significant variables were age (p = 0.015), liver dysfunction (p = 0.005), renal dysfunction (P < 0.001), altered consciousness (p = 0.049), and sepsis (p = 0.021). Logistic regression analysis showed that the factors associated with death in hospital were age over 70 years (Odds Ratio (OR) 6.6; 95% confidence interval (CI) 1.5 to 28.2; p = 0.011) and renal dysfunction (OR 15.4; 95% CI 3.8 to 62.8; p < 0.001). Univariate analysis of limb amputation showed that the significant variables were diabetes (p = 0.017) mellitus and sepsis (p = 0.001). Multivariable logistic regression analysis showed that the factors related to limb amputation were sepsis (OR 1.8; 95% CI 1.5 to 24.0; p = 0.013) and diabetes mellitus (OR 1.6; 95% CI 1.1 to 21.1; p = 0.038). For NSTIs of the upper extremity, advanced age and renal dysfunction are both associated with a higher rate of in-hospital mortality. Sepsis and diabetes mellitus are both associated with a higher rate of amputation. PMID:25371469

  1. Progressive upper limb prosthetics.

    PubMed

    Lake, Chris; Dodson, Robert

    2006-02-01

    The field of upper extremity prosthetics is a constantly changing arena as researchers and prosthetists strive to bridge the gap between prosthetic reality and upper limb physiology. With the further development of implantable neurologic sensing devices and targeted muscle innervation (discussed elsewhere in this issue), the challenge of limited input to control vast outputs promises to become a historical footnote in the future annals of upper limb prosthetics. Soon multidextrous terminal devices, such as that found in the iLimb system(Touch EMAS, Inc., Edinburgh, UK), will be a clinical reality (Fig. 22). Successful prosthetic care depends on good communication and cooperation among the surgeon, the amputee, the rehabilitation team, and the scientists harnessing the power of technology to solve real-life challenges. If the progress to date is any indication, amputees of the future will find their dreams limited only by their imagination. PMID:16517345

  2. Limb salvage surgery.

    PubMed

    Kadam, Dinesh

    2013-05-01

    The threat of lower limb loss is seen commonly in severe crush injury, cancer ablation, diabetes, peripheral vascular disease and neuropathy. The primary goal of limb salvage is to restore and maintain stability and ambulation. Reconstructive strategies differ in each condition such as: Meticulous debridement and early coverage in trauma, replacing lost functional units in cancer ablation, improving vascularity in ischaemic leg and providing stable walking surface for trophic ulcer. The decision to salvage the critically injured limb is multifactorial and should be individualised along with laid down definitive indications. Early cover remains the standard of care, delayed wound coverage not necessarily affect the final outcome. Limb salvage is more cost-effective than amputations in a long run. Limb salvage is the choice of procedure over amputation in 95% of limb sarcoma without affecting the survival. Compound flaps with different tissue components, skeletal reconstruction; tendon transfer/reconstruction helps to restore function. Adjuvant radiation alters tissue characters and calls for modification in reconstructive plan. Neuropathic ulcers are wide and deep often complicated by osteomyelitis. Free flap reconstruction aids in faster healing and provides superior surface for offloading. Diabetic wounds are primarily due to neuropathy and leads to six-fold increase in ulcerations. Control of infections, aggressive debridement and vascular cover are the mainstay of management. Endovascular procedures are gaining importance and have reduced extent of surgery and increased amputation free survival period. Though the standard approach remains utilising best option in the reconstruction ladder, the recent trend shows running down the ladder of reconstruction with newer reliable local flaps and negative wound pressure therapy. PMID:24501463

  3. Pathophysiology of sepsis and recent patents on the diagnosis, treatment and prophylaxis for sepsis.

    PubMed

    Okazaki, Yasumasa; Matsukawa, Akihiro

    2009-01-01

    Despite advances in the development of powerful antibiotics and intensive care unit, sepsis is still life threatening and the mortality rate remains unchanged for the past three decades. Recent prospective trials with biological response modifiers have shown a modest clinical benefit. The pathological basis of sepsis is initially an excessive inflammatory response against invading pathogens, leading to systemic inflammatory response syndrome (SIRS). Evidence reveals that a variety of inflammatory mediators orchestrate the intense inflammation through complicated cellular interactions. More recent data indicate that most septic patients survive this stage and then subjected to an immunoparalysis phase, termed compensatory anti-inflammatory response syndrome (CARS), which is more fatal than the initial phase. Sepsis is a complicated clinical syndrome with multiple physiologic and immunologic abnormalities. In this review, we summarize the recent understandings of the pathophysiology of sepsis, and introduce recent patents on diagnosis, treatment and prophylaxis for sepsis. PMID:19149743

  4. Accessories to Limb Regeneration.

    PubMed

    Han, Yanchao; Poss, Kenneth D

    2016-05-23

    In a recent issue of Nature, Nacu et al. (2016) identified FGF and HH ligands as interacting molecular influences that are necessary and sufficient to induce the formation of supernumerary limbs from blastemal tissue in axolotl salamanders. PMID:27219058

  5. Artificial limb connection

    NASA Technical Reports Server (NTRS)

    Owens, L. J.

    1974-01-01

    Connection simplifies and eases donning and removing artificial limb; eliminates harnesses and clamps; and reduces skin pressures by allowing bone to carry all tensile and part of compressive loads between prosthesis and stump. Because connection is modular, it is easily modified to suit individual needs.

  6. Mechanisms of Intestinal Barrier Dysfunction in Sepsis.

    PubMed

    Yoseph, Benyam P; Klingensmith, Nathan J; Liang, Zhe; Breed, Elise R; Burd, Eileen M; Mittal, Rohit; Dominguez, Jessica A; Petrie, Benjamin; Ford, Mandy L; Coopersmith, Craig M

    2016-07-01

    Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 h later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at 6 to 12 h. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13, and 15, Junctional Adhesion Molecule-A (JAM-A), occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 h after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis, whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 h after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis

  7. A blueprint for a sepsis protocol.

    PubMed

    Shapiro, Nathan I; Howell, Michael; Talmor, Daniel

    2005-04-01

    Despite numerous advances in medicine, sepsis remains an unconquered challenge. Although outcomes have improved slightly over decades, the unacceptably high mortality rate of 30%-50% for severe sepsis and septic shock continues. However, after years of unsuccessful clinical trials, several investigations over the last few years have reported survival benefit in the treatment of sepsis. Physicians now have several proven therapies to treat sepsis, but have yet to implement them on a widespread, systematic basis. This led 11 international professional societies spanning multiple specialties and continents to come together to create the Surviving Sepsis Campaign. The product of their work is an international effort organized to improve care of patients with sepsis and includes consensus, evidence-based guidelines for care that improves survival in septic patients, and an action plan for change. Given the clear role of early identification and treatment in stopping the sepsis cascade, therapy must start early in the emergency department (ED) and continue throughout the hospital course. The first of the recommendations by the Surviving Sepsis Campaign is the aggressive resuscitation strategy of early goal-directed therapy (EGDT). EGDT is reported to reduce absolute mortality by a staggering 16%. The use of recombinant activated protein C was demonstrated to confer a 6% absolute survival benefit. Steroid supplementation in adrenal insufficiency produced a 10% benefit. Additionally, early and appropriate use of antibiotics remains a cornerstone of therapy. Although no randomized trial will be performed, the effects are undisputed. Finally, although predominantly intensive care unit therapies, tight glucose control and low-tidal-volume ventilation strategies have also led to improved survival. Armed with these new therapies, the medical community must rise to this call to action. Clinicians must change the approach to this disease, as well as the way the septic patient is

  8. Early hominin limb proportions.

    PubMed

    Richmond, Brian G; Aiello, Leslie C; Wood, Bernard A

    2002-10-01

    Recent analyses and new fossil discoveries suggest that the evolution of hominin limb length proportions is complex, with evolutionary reversals and a decoupling of proportions within and between limbs. This study takes into account intraspecific variation to test whether or not the limb proportions of four early hominin associated skeletons (AL 288-1, OH 62, BOU-VP-12/1, and KNM-WT 15000) can be considered to be significantly different from one another. Exact randomization methods were used to compare the differences between pairs of fossil skeletons to the differences observed between all possible pairs of individuals within large samples of Gorilla gorilla, Pan troglodytes, Pongo pygmaeus, and Homo sapiens. Although the difference in humerofemoral proportions between OH 62 and AL 288-1 does not exceed variation in the extant samples, it is rare. When humerofemoral midshaft circumferences are compared, the difference between OH 62 and AL 288-1 is fairly common in extant species. This, in combination with error associated with the limb lengths estimates, suggests that it may be premature to consider H. (or Australopithecus) habilis as having more apelike limb proportions than those in A. afarensis. The humerofemoral index of BOU-VP-12/1 differs significantly from both OH 62 and AL 288-1, but not from KNM-WT 15000. Published length estimates, if correct, suggest that the relative forearm length of BOU-VP-12/1 is unique among hominins, exceeding those of the African apes and resembling the proportions in Pongo. Evidence that A. afarensis exhibited a less apelike upper:lower limb design than A. africanus (and possibly H. habilis) suggests that, if A. afarensis is broadly ancestral to A. africanus, the latter did not simply inherit primitive morphology associated with arboreality, but is derived in this regard. The fact that the limb proportions of OH 62 (and possibly KNM-ER 3735) are no more human like than those of AL 288-1 underscores the primitive body design of H

  9. 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

  10. Neuromuscular Dysfunction in Experimental Sepsis and Glutamine

    PubMed Central

    Çankayalı, İlkin; Boyacılar, Özden; Demirağ, Kubilay; Uyar, Mehmet; Moral, Ali Reşat

    2016-01-01

    Background: Electrophysiological studies show that critical illness polyneuromyopathy appears in the early stage of sepsis before the manifestation of clinical findings. The metabolic response observed during sepsis causes glutamine to become a relative essential amino acid. Aims: We aimed to assess the changes in neuromuscular transmission in the early stage of sepsis after glutamine supplementation. Study Design: Animal experimentation. Methods: Twenty male Sprague-Dawley rats were randomized into two groups. Rats in both groups were given normal feeding for one week. In the study group, 1 g/kg/day glutamine was added to normal feeding by feeding tube for one week. Cecal ligation and perforation (CLP) surgery was performed at the end of one week. Before and 24 hours after CLP, compound muscle action potentials were recorded from the gastrocnemius muscle. Results: Latency measurements before and 24 hours after CLP were 0.68±0.05 ms and 0.80±0.09 ms in the control group and 0.69±0.07 ms and 0.73±0.07 ms in the study group (p<0.05). Conclusion: Since enteral glutamine prevented compound muscle action potentials (CMAP) latency prolongation in the early phase of sepsis, it was concluded that enteral glutamine replacement might be promising in the prevention of neuromuscular dysfunction in sepsis; however, further studies are required. PMID:27308070

  11. Current concept of abdominal sepsis: WSES position paper

    PubMed Central

    2014-01-01

    Although sepsis is a systemic process, the pathophysiological cascade of events may vary from region to region. Abdominal sepsis represents the host’s systemic inflammatory response to bacterial peritonitis. It is associated with significant morbidity and mortality rates, and is the second most common cause of sepsis-related mortality in the intensive care unit. The review focuses on sepsis in the specific setting of severe peritonitis. PMID:24674057

  12. Performance improvement in the management of sepsis.

    PubMed

    Schorr, Christa

    2011-03-01

    Sepsis guidelines, although creating a base to allow change in health care practitioner behavior, do not, in and of themselves, effect change. Change only comes with institution of a PI program, converting a core of key goals of guideline recommendations to quality indicators, and giving feedback on performance. These quality indicators are tracked before or during (recommended approach) initiation of hospital-wide education to evaluate baseline performance. When combining multispecialty and multidisciplinary champions in the ED, hospital wards, ICU, and hospital administrative leadership with timely performance feedback, case failure analysis, and re-education, an opportunity to succeed in decreasing mortality in severe sepsis can be achieved. Sepsis bundle indicators require updating as new evidence emerges and new guidelines are published.(30,31) PMID:21316576

  13. Mitochondrial dysfunction and resuscitation in sepsis.

    PubMed

    Ruggieri, Albert J; Levy, Richard J; Deutschman, Clifford S

    2010-07-01

    Sepsis is among the most common causes of death in patients in intensive care units in North America and Europe. In the United States, it accounts for upwards of 250,000 deaths each year. Investigations into the pathobiology of sepsis have most recently focused on common cellular and subcellular processes. One possibility would be a defect in the production of energy, which translates to an abnormality in the production of adenosine triphosphate and therefore in the function of mitochondria. This article presents a clear role for mitochondrial dysfunction in the pathogenesis and pathophysiology of sepsis. What is less clear is the teleology underlying this response. Prolonged mitochondrial dysfunction and impaired biogenesis clearly are detrimental. However, early inhibition of mitochondrial function may be adaptive. PMID:20643307

  14. Role of immunoglobulins in neonatal sepsis

    PubMed Central

    Capasso, L; Borrelli, AC; Cerullo, J; Pisanti, R; Figliuolo, C; Izzo, F; Paccone, M; Ferrara, T; Lama, S; Raimondi, F

    2015-01-01

    Neonates, especially VLBW, are at high risk for sepsis related morbidity and mortality for immaturity of their immune system and invasive NICU practices. The paucity of immunoglobulins in preterm neonates consequently to the immaturity of immune system contributes to their high risk for systemic infection. The use of intravenous IgM enriched immunoglobulins, with higher antimicrobial activity than standard IgG, has been demonstrated in a retrospective study to reduce short term mortality in VLBW infant with proven sepsis. Larger, randomized prospective trials given the enormous burden of morbidity and mortality imposed by neonatal sepsis should urgently be addressed not only to validate this results but also to tailor the optimal scheme of treatment. PMID:25674546

  15. 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

  16. 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

  17. Host innate immune responses to sepsis

    PubMed Central

    Wiersinga, Willem Joost; Leopold, Stije J; Cranendonk, Duncan R; van der Poll, Tom

    2014-01-01

    The immune response to sepsis can be seen as a pattern recognition receptor-mediated dysregulation of the immune system following pathogen invasion in which a careful balance between inflammatory and anti-inflammatory responses is vital. Invasive infection triggers both pro-inflammatory and anti-inflammatory host responses, the magnitude of which depends on multiple factors, including pathogen virulence, site of infection, host genetics, and comorbidities. Toll-like receptors, the inflammasomes, and other pattern recognition receptors initiate the immune response after recognition of danger signals derived from microorganisms, so-called pathogen-associated molecular patterns or derived from the host, so-called danger-associated molecular patterns. Further dissection of the role of host–pathogen interactions, the cytokine response, the coagulation cascade, and their multidirectional interactions in sepsis should lead toward the development of new therapeutic strategies in sepsis. PMID:23774844

  18. An Evidence Based Approach to Sepsis: Educational Program

    ERIC Educational Resources Information Center

    Perez, Dolores

    2015-01-01

    Evidence-based guidelines for recognizing and treating sepsis have been available for decades, yet healthcare providers do not adhere to the recommendations. Sepsis can progress rapidly if not recognized early. Literature reports reveal that sepsis is the leading cause of death in non-cardiac intensive care units (ICUs), and it is one of the most…

  19. Fluid Resuscitation in Sepsis: Reexamining the Paradigm

    PubMed Central

    Tirupakuzhi Vijayaraghavan, Bharath Kumar; Cove, Matthew Edward

    2014-01-01

    Sepsis results in widespread inflammatory responses altering homeostasis. Associated circulatory abnormalities (peripheral vasodilation, intravascular volume depletion, increased cellular metabolism, and myocardial depression) lead to an imbalance between oxygen delivery and demand, triggering end organ injury and failure. Fluid resuscitation is a key part of treatment, but there is little agreement on choice, amount, and end points for fluid resuscitation. Over the past few years, the safety of some fluid preparations has been questioned. Our paper highlights current concerns, reviews the science behind current practices, and aims to clarify some of the controversies surrounding fluid resuscitation in sepsis. PMID:25180196

  20. The Use of Fluids in Sepsis.

    PubMed

    Avila, Audrey A; Kinberg, Eliezer C; Sherwin, Nomi K; Taylor, Robinson D

    2016-01-01

    Sepsis is a systemic inflammatory response to severe infection causing significant morbidity and mortality that costs the health care system $20.3 billion annually within the United States. It is well established that fluid resuscitation is a central component of sepsis management; however, to date there is no consensus as to the ideal composition of fluid used for resuscitation. In this review, we discuss the progression of clinical research comparing various fluids, as well as the historical background behind fluid selection for volume resuscitation. We conclude that the use of balanced fluids, such as Ringer's Lactate, seems very promising but further research is needed to confirm their role. PMID:27081589

  1. [Bacterial meningitis in patients with sepsis syndrome].

    PubMed

    Olejnik, Z; Janeczko, J; Lipowski, D; Przyjałkowski, W; Strzelecki, R; Romanowska, B; Pogorzelska, E

    1994-01-01

    The authors discuss problems connected with diagnosis, management and treatment of bacterial meningitis among patients with the sepsis syndrome. Considering secondary organ changes bacterial meningitis belongs to the severest one and as a life-threathing sequel of sepsis demands immediate use of proper casual treatment. The authors show the therapeutic difficulties in this group of patients particularly when the etiological organism is unknown. They discuss this problems and present their own schemes of tretment. They indicate the value of passive immunotherapy and surgical removal of the primary source of infection. They emphasize final result depends on secondary organ changes, age, immunity of patient and the kind of etiological agent. PMID:7938619

  2. Hepatosplanchnic circulation in cirrhosis and sepsis

    PubMed Central

    Prin, Meghan; Bakker, Jan; Wagener, Gebhard

    2015-01-01

    Hepatosplanchnic circulation receives almost half of cardiac output and is essential to physiologic homeostasis. Liver cirrhosis is estimated to affect up to 1% of populations worldwide, including 1.5% to 3.3% of intensive care unit patients. Cirrhosis leads to hepatosplanchnic circulatory abnormalities and end-organ damage. Sepsis and cirrhosis result in similar circulatory changes and resultant multi-organ dysfunction. This review provides an overview of the hepatosplanchnic circulation in the healthy state and in cirrhosis, examines the signaling pathways that may play a role in the physiology of cirrhosis, discusses the physiology common to cirrhosis and sepsis, and reviews important issues in management. PMID:25759525

  3. Regeneration inducers in limb regeneration.

    PubMed

    Satoh, Akira; Mitogawa, Kazumasa; Makanae, Aki

    2015-08-01

    Limb regeneration ability, which can be observed in amphibians, has been investigated as a representative phenomenon of organ regeneration. Recently, an alternative experimental system called the accessory limb model was developed to investigate early regulation of amphibian limb regeneration. The accessory limb model contributed to identification of limb regeneration inducers in urodele amphibians. Furthermore, the accessory limb model may be applied to other species to explore universality of regeneration mechanisms. This review aims to connect the insights recently gained to emboss universality of regeneration mechanisms among species. The defined molecules (BMP7 (or2) + FGF2 + FGF8) can transform skin wound healing to organ (limb) regeneration responses. The same molecules can initiate regeneration responses in some species. PMID:26100345

  4. [Limb Scattering Data Analysis

    NASA Technical Reports Server (NTRS)

    Loughman, Robert; Herman, Benjamin

    2001-01-01

    The primary purpose of this grant was to support analysis of the limb scattering data taken during the 1997 flight of the SOLSE (Shuttle Ozone Limb Sounding Experiment) and LORE (Limb Ozone Retrieval Experiment) instruments. Work was done to assess the performance of the retrieval algorithms for cloudy and clear sky cases in preparation for a poster presentation. The nadir-viewing data were also compared to coincident GOME (Global Ozone Monitoring Experiment) data and to radiative transfer calculations. An algorithm similar to the TOMS (Total Ozone Mapping Spectrometer) ozone retrieval algorithm was developed to infer the ozone column amount from the SOLSE nadir data. Comparison with coincident TOMS ozone column data confirmed that column ozone could be derived successfully from SOLSE nadir radiances, and also revealed significant changes in the SOLSE wavelength resolution and absolute radiometric calibration that were subsequently confirmed by comparing the post-flight instrument characterization to the pre-flight characterization, indicating a potentially useful method for monitoring instrument behavior in-flight.

  5. Therapeutic Targets in Sepsis: Past, Present, and Future.

    PubMed

    Seeley, Eric J; Bernard, Gordon R

    2016-06-01

    Antibiotics and fluids have been standard treatment for sepsis since World War II. Many molecular mediators of septic shock have since been identified. In models of sepsis, blocking these mediators improved organ injury and decreased mortality. Clinical trials, however, have failed. The absence of new therapies has been vexing to clinicians, clinical researchers, basic scientists, and the pharmaceutical industry. This article examines the evolution of sepsis therapy and theorizes about why so many well-reasoned therapies have not worked in human trials. We review new molecular targets for sepsis and examine trial designs that might lead to successful treatments for sepsis. PMID:27229636

  6. [An inquiry into the relevant issues about burn sepsis].

    PubMed

    Zhang, Qin; Liao, Zhenjiang

    2014-02-01

    Since the definition of sepsis was proposed in Chest by American College of Chest Physicians and Society of Critical Care Medicine in 1992, researches on burn sepsis have focused on the regulation of immune-inflammation response resulting in minimizing tissue injury resulted from excessive inflammatory response. Treatment of sepsis should focus on effect of early circulation oxygenation support in preventing and treating multiple organ dysfunction. The hypothesis of producing a hibernation-like state which might prevent multiple organ dysfunction in patients with sepsis provides us a new therapeutic strategy in protecting organs in the early stage of sepsis in future. PMID:24684982

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

    PubMed Central

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

    2015-01-01

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

  8. Intra-abdominal sepsis after hepatic resection.

    PubMed Central

    Pace, R F; Blenkharn, J I; Edwards, W J; Orloff, M; Blumgart, L H; Benjamin, I S

    1989-01-01

    One hundred and thirty hepatic resections performed over an 8-year period were reviewed for evidence of postoperative intra-abdominal sepsis. Of 126 patients who survived for more than 24 hours after operation, 36 developed culture positive intra-abdominal collections (28.6%). Significant independent variables associated with the development of intra-abdominal sepsis were diagnoses of trauma or cholangiocarcinoma, and the need for reoperation to control hemorrhage during the postoperative period. Before 1984, infected fluid collections were treated predominantly by operative drainage, but this has largely been replaced by percutaneous methods, which have proven effective in most cases. Eighteen (50%) of the infections were caused by a mixed bacterial culture, with Streptococcus faecalis, Staphylococcus epidermidis, Staphylococcus aureus and Escherichia coli being the most common isolates. Six patients with clinical signs of sepsis had a sterile fluid collection drained with complete relief of symptoms. This review suggests that intra-abdominal sepsis is a frequent complication after hepatic resection, and can often be managed successfully by nonoperative percutaneous drainage. PMID:2493775

  9. [Innate immunity, Toll receptor and sepsis].

    PubMed

    Carrillo-Esper, Raúl

    2003-01-01

    The innate immune response is the first line of defense against infection. Toll-like receptors (TLRs) recognize bacterial lipopolysaccharide and other pathogen-associated molecular patterns (PAMPs). Intracellular signals initiated by interaction between Toll receptors and specific PAMPs results in inflammatory response. Sepsis and septic shock are the result of an exaggerated inflammatory systemic response induced by innate immune dysregulation. PMID:14617415

  10. Clinical analysis of cases of neonatal Streptococcus agalactiae sepsis.

    PubMed

    Zeng, S J; Tang, X S; Zhao, W L; Qiu, H X; Wang, H; Feng, Z C

    2016-01-01

    With the advent of antibiotic resistance, pathogenic bacteria have become a major threat in cases of neonatal sepsis; however, guidelines for treatment have not yet been standardized. In this study, 15 cases of neonatal Streptococcus agalactiae sepsis from our hospital were retrospectively analyzed. Of these, nine cases showed early-onset and six cases showed late-onset sepsis. Pathogens were characterized by genotyping and antibiotic sensitivity tests on blood cultures. Results demonstrated that in cases with early-onset sepsis, clinical manifestations affected mainly the respiratory tract, while late-onset sepsis was accompanied by intracranial infection. Therefore, we suggest including a cerebrospinal fluid examination when diagnosing neonatal sepsis. Bacterial genotyping indicated the bacteria were mainly type Ib, Ia, and III S. agalactiae. We recommend treatment with penicillin or ampicillin, since bacteria were resistant to clindamycin and tetracycline. In conclusion, our results provide valuable information for the clinical treatment of S. agalactiae sepsis in neonatal infants. PMID:27323190

  11. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    PubMed Central

    Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

    2016-01-01

    IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a

  12. Hospitalization Type and Subsequent Severe Sepsis

    PubMed Central

    Dickson, Robert P.; Rogers, Mary A. M.; Langa, Kenneth M.; Iwashyna, Theodore J.

    2015-01-01

    Rationale: Hospitalization is associated with microbiome perturbation (dysbiosis), and this perturbation is more severe in patients treated with antimicrobials. Objectives: To evaluate whether hospitalizations known to be associated with periods of microbiome perturbation are associated with increased risk of severe sepsis after hospital discharge. Methods: We studied participants in the U.S. Health and Retirement Study with linked Medicare claims (1998–2010). We measured whether three hospitalization types associated with increasing severity of probable dysbiosis (non–infection-related hospitalization, infection-related hospitalization, and hospitalization with Clostridium difficile infection [CDI]) were associated with increasing risk for severe sepsis in the 90 days after hospital discharge. We used two study designs: the first was a longitudinal design with between-person comparisons and the second was a self-controlled case series design using within-person comparison. Measurements and Main Results: We identified 43,095 hospitalizations among 10,996 Health and Retirement Study–Medicare participants. In the 90 days following non–infection-related hospitalization, infection-related hospitalization, and hospitalization with CDI, adjusted probabilities of subsequent admission for severe sepsis were 4.1% (95% confidence interval [CI], 3.8–4.4%), 7.1% (95% CI, 6.6–7.6%), and 10.7% (95% CI, 7.7–13.8%), respectively. The incidence rate ratio (IRR) of severe sepsis was 3.3-fold greater during the 90 days after hospitalizations than during other observation periods. The IRR was 30% greater after an infection-related hospitalization versus a non–infection-related hospitalization. The IRR was 70% greater after a hospitalization with CDI than an infection-related hospitalization without CDI. Conclusions: There is a strong dose–response relationship between events known to result in dysbiosis and subsequent severe sepsis hospitalization that is not present

  13. Objective Sepsis Surveillance Using Electronic Clinical Data

    PubMed Central

    Rhee, Chanu; Kadri, Sameer; Huang, Susan S.; Murphy, Michael V.; Li, Lingling; Platt, Richard; Klompas, Michael

    2016-01-01

    OBJECTIVE To compare the accuracy of surveillance of severe sepsis using electronic health record clinical data vs claims and to compare incidence and mortality trends using both methods. DESIGN We created an electronic health record–based surveillance definition for severe sepsis using clinical indicators of infection (blood culture and antibiotic orders) and concurrent organ dysfunction (vasopressors, mechanical ventilation, and/or abnormal laboratory values). We reviewed 1,000 randomly selected medical charts to characterize the definition’s accuracy and stability over time compared with a claims-based definition requiring infection and organ dysfunction codes. We compared incidence and mortality trends from 2003–2012 using both methods. SETTING Two US academic hospitals. PATIENTS Adult inpatients. RESULTS The electronic health record–based clinical surveillance definition had stable and high sensitivity over time (77% in 2003–2009 vs 80% in 2012, P=.58) whereas the sensitivity of claims increased (52% in 2003–2009 vs 67% in 2012, P=.02). Positive predictive values for claims and clinical surveillance definitions were comparable (55% vs 53%, P=.65) and stable over time. From 2003 to 2012, severe sepsis incidence imputed from claims rose by 72% (95% CI, 57%–88%) and absolute mortality declined by 5.4% (95% CI, 4.6%–6.7%). In contrast, incidence using the clinical surveillance definition increased by 7.7% (95% CI, −1.1% to 17%) and mortality declined by 1.7% (95% CI, 1.1%–2.3%). CONCLUSIONS Sepsis surveillance using clinical data is more sensitive and more stable over time compared with claims and can be done electronically. This may enable more reliable estimates of sepsis burden and trends. PMID:26526737

  14. [Initial antibiotic therapy of neonatal sepsis].

    PubMed

    Jesić, Milos; Jesić, Maja; Maglajlić, Svjetlana; Lukac, Marija; Sindjić, Sanja; Vujović, Dragana; Grković, Slobodanka

    2004-10-01

    It is certain that in the past the types of bacterial agents responsible for neonatal sepsis and their sensitivity to antibiotics were not the same in all historical periods. However, the reports confirming the conclusion have been published only in the last three years. According to these facts, the bacterial causes of neonatal sepsis were analyzed in patients treated at the University children's hospital in Belgrade (S&M) as well as their sensitivity to antibiotics to determine the most effective initial therapy. Between January 2001 and June 2004, 35 neonates, aged from 1-30 days, with positive blood culture were treated. Gram-negative bacteria were the cause of sepsis in 57% of patients (Pseudomonas--20%, Klebsiella--20%, E. coli--8.5%, Acinetobacter--8.5%), gram-positive in 43% (coagulase-negative Staphylococci--14%, Staphylococcus epidermidis--14%, Staphylococcus aureus--9%, Streptococcus group B--3%, Listeria monocytogenes--3%). The bacteria were the most sensitive to carbapenems (85-89%), amikacin (68%), third-generation cephalosporins (47-50%), while the sensitivity to gentamicin was less than expected (48.5%). Sensitivity to ampicillin (8%) confirmed a high level of resistance to this antibiotic. All isolated Staphylococci were sensitive to vancomycin, and the overall methicillin resistance was 46%. Combined cefotaxime and amikacin therapy was the most effective of all suggested initial combinations of antibiotics (74%). The sensitivity to all other combinations of antibiotics was 51-71%. The most adequate initial combination of antibiotics for the treatment of neonatal sepsis is cefotaxime plus amikacin. The most adequate antibiotic for the treatment of nosocomial neonatal sepsis is carbapenem. PMID:15615466

  15. A tale of two soles: sociomechanical and biomechanical considerations in diabetic limb salvage and amputation decision-making in the worst of times

    PubMed Central

    Fiorito, Joseph; Trinidad-Hernadez, Magdiel; Leykum, Brian; Smith, Derek; Mills, Joseph L.; Armstrong, David G.

    2012-01-01

    Foot ulcerations complicated by infection are the major cause of limb loss in people with diabetes. This is especially true in those patients with severe sepsis. Determining whether to amputate or attempt to salvage a limb often requires in depth evaluation of each individual patient's physical, mental, and socioeconomic status. The current report presents and juxtaposes two similar patients, admitted to the same service at the same time with severe diabetic foot infections complicated by sepsis. We describe in detail the similarities and differences in the clinical presentation, extent of infection, etiology, and socioeconomic concerns that ultimately led to divergent clinical decisions regarding the choices of attempting diabetic limb salvage versus primary amputation and prompt rehabilitation. PMID:23050063

  16. Polymerase chain reaction in rapid diagnosis of neonatal sepsis.

    PubMed

    Yadav, Ashok K; Wilson, C G; Prasad, P L; Menon, P K

    2005-07-01

    In a prospective study a total of hundred neonates who fulfilled the American College of Obstetrics and Gynecology's (ACOG) criteria for probable sepsis admitted to NICU of tertiary care armed forces hospital were investigated for evidence of sepsis. The investigation protocol included sepsis screen, blood culture and 1 mL of venous blood for molecular analysis by polymerase chain reaction (PCR) for bacterial DNA component encoding 16 s RNA in all cases. 100 newborns with probable sepsis were studied to evaluate the molecular diagnosis of sepsis using PCR amplification of 16 S RNA in newborns with risk factors for sepsis or those who have clinical evidence of sepsis. We compared the results of PCR with blood culture and other markers of sepsis screen (total leucocyte count (TLC), absolute neutrophil count (ANC), immature/total neutrophil count ratio (I/T ratio), peripheral blood smear, micro ESR and C reactive protein (CRP). Controls consisted of 30 normal healthy newborns with no overt evidence of sepsis. Sepsis screen was positive in 24 (24%) of cases in study group with sensitivity and specificity of 100% and 83.5% respectively. Blood culture was positive in 09(9%t) with sensitivity of 69.2% and specificity of 100%. PCR was positive in 13(13%) of cases (9% are both blood culture and sepsis screen positive and 4% are positive by sepsis screen); the sensitivity of PCR was 100% and specificity was 95.6%. Blood culture is the most reliable method for diagnosis of neonatal sepsis. Polymerase chain reaction is useful and superior to blood culture for early diagnosis of sepsis in neonates. PMID:16085969

  17. Alterations of T helper lymphocyte subpopulations in sepsis, severe sepsis, and septic shock: a prospective observational study.

    PubMed

    Li, Jia; Li, Ming; Su, Longxiang; Wang, Huijuan; Xiao, Kun; Deng, Jie; Jia, Yanhong; Han, Gencheng; Xie, Lixin

    2015-01-01

    Circulating lymphocyte number was significantly decreased in patients with sepsis. However, it remains unknown which severity phase (sepsis, severe sepsis, and septic shock) does it develop and what happen on each subpopulation. Eight patients with differing severities of sepsis (31 sepses, 33 severe sepses, and 16 septic shocks) were enrolled. Quantitative real-time polymerase chain reaction (RT-PCR) of Th1, Th2, and Th17; regulatory T (Treg) cell-specific transcription factor T-bet; GATA-3; RORgammat (RORγt); forkhead box P3 (FOXP3); and IL-17 mRNA were performed, and the enzyme-linked immunosorbent assay (ELISA) was used to detect serum interferon (IFN)-γ, IL-4, and IL-10. In this study, the Th1, Th2, Treg transcription factors, and related cytokines IFN-γ, IL-4, and IL-10 levels of sepsis and severe sepsis patients in peripheral blood were significantly higher than those of the normal controls. Except for IL-17, the T-bet, GATA-3, and IFN-γ levels of septic shock patients were lower than those of sepsis patients. We also observed that the proportions of Th17/Treg in the sepsis and septic shock groups were inversed. From the above, the inflammatory response especially the adaptive immune response is still activated in sepsis and severe sepsis, but significant immunosuppression was developed in septic shock. In addition, the proportion of Th17/Treg inversed may be associated with the illness aggravation of patients with sepsis. PMID:25403265

  18. [Therapy of phantom limb pain].

    PubMed

    Schwarzer, Andreas; Zenz, Michael; Maier, Christoph

    2009-03-01

    About 80 % of all extremity amputations suffer from phantom limb pain following the operation. In this context, it is important to differentiate between painful phantom limb sensations, non-painful phantom limb sensations and residual limb pain. The pathophysiology of phantom limb pain is not fully understood. Current research findings ascribe a major pathophysiological role to cortical changes as well as a disturbed body perception. Peripheral and spinal mechanisms appear less relevant in the development of phantom limb pain. An essential part of the therapy is the pharmacological treatment with antidepressants, anticonvulsives and opioids. Another significant aspect of therapy is senso-motory training, important to mention here would be mirror therapy, lateralisation and motor imaging. In case of an elective amputation, an epidural or axiliar plexus catheter should be considered prior to the amputation. The perioperative treatment with ketamine is debated. PMID:19266417

  19. Limb lengthening in achondroplasia

    PubMed Central

    Chilbule, Sanjay K; Dutt, Vivek; Madhuri, Vrisha

    2016-01-01

    Background: Stature lengthening in skeletal dysplasia is a contentious issue. Specific guidelines regarding the age and sequence of surgery, methods and extent of lengthening at each stage are not uniform around the world. Despite the need for multiple surgeries, with their attendant complications, parents demanding stature lengthening are not rare, due to the social bias and psychological effects experienced by these patients. This study describes the outcome and complications of extensive stature lengthening performed at our center. Materials and Methods: Eight achondroplasic and one hypochondroplasic patient underwent bilateral transverse lengthening for tibiae, humeri and femora. Tibia lengthening was carried out using a ring fixator and bifocal corticotomy, while a monolateral pediatric limb reconstruction system with unifocal corticotomy was used for the femur and humerus. Lengthening of each bone segment, height gain, healing index and complications were assessed. Subgroup analysis was carried out to assess the effect of age and bone segment on the healing index. Results: Nine patients aged five to 25 years (mean age 10.2 years) underwent limb lengthening procedures for 18 tibiae, 10 femora and 8 humeri. Four patients underwent bilateral lengthening of all three segments. The mean length gain for the tibia, femur and humerus was 15.4 cm (100.7%), 9.9 cm (52.8%) and 9.6 cm (77.9%), respectively. Healing index was 25.7, 25.6 and 20.6 days/cm, respectively, for the tibia, femur and humerus. An average of 33.3% height gain was attained. Lengthening of both tibia and femur added to projected height achieved as the 3rd percentile of standard height in three out of four patients. In all, 33 complications were encountered (0.9 complications per segment). Healing index was not affected by age or bone segment. Conclusion: Extensive limb lengthening (more than 50% over initial length) carries significant risk and should be undertaken only after due consideration. PMID

  20. Lipotyphla limb myology comparison.

    PubMed

    Neveu, Pauline; Gasc, Jean-Pierre

    2002-05-01

    Fore- and hindlimb muscles were dissected in four species of Lipotyphla: the western European hedgehog Erinaceus europaeus (Erinaceidae, Erinaceinae); the moonrat Echinosorex gymnura (Erinaceidae, Hylomyinae or Galericinae); the tailless tenrec Tenrec ecaudatus (Tenrecidae, Tenrecinae); and the common European white-toothed shrew Crocidura russula (Soricidae, Soricinae). This work completely reviews the limb musculature of these walking mammals. Twelve myological characters were evaluated in order to disclose phylogenetic relationships. The cladogram obtained supported previous ones based on cranial and dental characters. This study shows that myological characters are valuable in phylogenetic analyses. PMID:11921044

  1. Improving the management of sepsis in a district general hospital by implementing the 'Sepsis Six' recommendations.

    PubMed

    Kumar, Prashant; Jordan, Mark; Caesar, Jenny; Miller, Sarah

    2015-01-01

    Sepsis is a common condition with a major global impact on healthcare resources and expenditure. The Surviving Sepsis Campaign has been vigorous in promoting internationally recognised pathways to improve the management of septic patients and decrease mortality. However, translating recommendations into practice is a challenging and complex task that requires a multi-faceted approach with sustained engagement from local stakeholders. Whilst working at a district general hospital in New Zealand, we were concerned by the seemingly inconsistent management of septic patients, often leading to long delays in the initiation of life-saving measures such as antibiotic, fluid, and oxygen administration. In our hospital there were no clear systems, protocols or guidelines in place for identifying and managing septic patients. We therefore launched the Sepsis Six resuscitation bundle of care in our hospital in an attempt to raise awareness amongst staff and improve the management of septic patients. We introduced a number of simple low-cost interventions that included educational sessions for junior doctors and nursing staff, as well as posters and modifications to phlebotomy trolleys that acted as visual reminders to implement the Sepsis Six bundle. Overall, we found there to a be a steady improvement in the delivery of the Sepsis Six bundle in septic patients with 63% of patients receiving appropriate care within one hour, compared to 29% prior to our interventions. However this did not translate to an improvement in patient mortality. This project forms part of an on going process to instigate a fundamental culture change among local healthcare professionals regarding the management of sepsis. Whilst we have demonstrated improved implementation of the Sepsis Six bundle, the key challenge remains to ensure that momentum of this project continues and forms a platform for sustainable clinical improvement in the long term. PMID:26734403

  2. 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

  3. Sirtuin-2 Regulates Sepsis Inflammation in ob/ob Mice

    PubMed Central

    Wang, Xianfeng; Buechler, Nancy L.; Martin, Ayana; Wells, Jonathan; Yoza, Barbara; McCall, Charles E.; Vachharajani, Vidula

    2016-01-01

    Objective Obesity increases morbidity and resource utilization in sepsis patients. Sepsis transitions from early/hyper-inflammatory to late/hypo-inflammatory phase. Majority of sepsis-mortality occurs during the late sepsis; no therapies exist to treat late sepsis. In lean mice, we have shown that sirtuins (SIRTs) modulate this transition. Here, we investigated the role of sirtuins, especially the adipose-tissue abundant SIRT-2 on transition from early to late sepsis in obese with sepsis. Methods Sepsis was induced using cecal ligation and puncture (CLP) in ob/ob mice. We measured microvascular inflammation in response to lipopolysaccharide/normal saline re-stimulation as a “second-hit” (marker of immune function) at different time points to track phases of sepsis in ob/ob mice. We determined SIRT-2 expression during different phases of sepsis. We studied the effect of SIRT-2 inhibition during the hypo-inflammatory phase on immune function and 7-day survival. We used a RAW264.7 (RAW) cell model of sepsis for mechanistic studies. We confirmed key findings in diet induced obese (DIO) mice with sepsis. Results We observed that the ob/ob-septic mice showed an enhanced early inflammation and a persistent and prolonged hypo-inflammatory phase when compared to WT mice. Unlike WT mice that showed increased SIRT1 expression, we found that SIRT2 levels were increased in ob/ob mice during hypo-inflammation. SIRT-2 inhibition in ob/ob mice during the hypo-inflammatory phase of sepsis reversed the repressed microvascular inflammation in vivo via activation of endothelial cells and circulating leukocytes and significantly improved survival. We confirmed the key finding of the role of SIRT2 during hypo-inflammatory phase of sepsis in this project in DIO-sepsis mice. Mechanistically, in the sepsis cell model, SIRT-2 expression modulated inflammatory response by deacetylation of NFκBp65. Conclusion SIRT-2 regulates microvascular inflammation in obese mice with sepsis and may

  4. 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

  5. National variation in United States sepsis mortality: a descriptive study

    PubMed Central

    2010-01-01

    Background The regional distribution of a disease may provide important insights regarding its pathophysiology, risk factors and clinical care. While sepsis is a prominent cause of death in the United States (US), few studies have examined regional variations with this malady. We identified the national variation in sepsis deaths in the US. We conducted a descriptive analysis of 1999-2005 national vital statistics data from the National Center for Health Statistics summarized at the state-level. We defined sepsis deaths as deaths attributed to an infection, classified according to the International Classification of Diseases, Version 10. We calculated national and state age-adjusted sepsis-attributed mortality rates. Results National age-adjusted sepsis mortality was 65.5 per 100,000 persons (95% CI: 65.8 - 66.0). State level sepsis mortality varied more than two-fold (range 41 to 88.6 per 100,000 persons; median 60.8 per 100,000, IQR 53.9-74.4 per 100,000). A cluster extending from the Southeastern to the mid-Atlantic US encompassed states with the highest sepsis mortality. Conclusions Sepsis mortality varies across the US. The states with highest sepsis mortality form a contiguous cluster in the Southeastern and mid-Atlantic US. These observations highlight unanswered questions regarding the characteristics and care of sepsis. PMID:20156361

  6. 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

  7. Phantom limb pain after lower limb trauma: origins and treatments.

    PubMed

    Foell, Jens; Bekrater-Bodmann, Robin; Flor, Herta; Cole, Jonathan

    2011-12-01

    Phantom sensations, that is, sensations perceived in a body part that has been lost, are a common consequence of accidental or clinical extremity amputations. Most amputation patients report a continuing presence of the limb, with some describing additional sensations such as numbness, tickling, or cramping of the phantom limb. The type, frequency, and stability of these phantom sensations can vary immensely. The phenomenon of painful phantom sensations, that is, phantom limb pain, presents a challenge for practitioners and researchers and is often detrimental to the patient's quality of life. In addition to the use of conventional therapies for chronic pain disorders, recent years have seen the development of novel treatments for phantom limb pain, based on an increasing body of research on neurophysiological changes after amputation. This article describes the current state of research in regard to the demographics, causal factors, and treatments of phantom limb pain. PMID:22184752

  8. Sepsis management: An evidence-based approach.

    PubMed

    Baig, Muhammad Akbar; Shahzad, Hira; Jamil, Bushra; Hussain, Erfan

    2016-03-01

    The Surviving Sepsis Campaign (SSC) guidelines have outlined an early goal directed therapy (EGDT) which demonstrates a standardized approach to ensure prompt and effective management of sepsis. Having said that, there are barriers associated with the application of evidence-based practice, which often lead to an overall poorer adherence to guidelines. Considering the global burden of disease, data from low- to middle-income countries is scarce. Asia is the largest continent but most Asian countries do not have a well-developed healthcare system and compliance rates to resuscitation and management bundles are as low as 7.6% and 3.5%, respectively. Intensive care units are not adequately equipped and financial concerns limit implementation of expensive treatment strategies. Healthcare policy-makers should be notified in order to alleviate financial restrictions and ensure delivery of standard care to septic patients. PMID:26968289

  9. Sepsis in the severely immunocompromised patient.

    PubMed

    Kalil, Andre C; Opal, Steven M

    2015-06-01

    The prevention and treatment of sepsis in the immunocompromised host present a challenging array of diagnostic and management issues. The neutropenic patient has a primary defect in innate immune responses and is susceptible to conventional and opportunistic pathogens. The solid organ transplant patient has a primary defect in adaptive immunity and is susceptible to a myriad of pathogens that require an effective cellular immune response. Risk for infections in organ transplant recipients is further complicated by mechanical, vascular, and rejection of the transplanted organ itself. The immune suppressed state can modify the cardinal signs of inflammation, making accurate and rapid diagnosis of infection and sepsis difficult. Empiric antimicrobial agents can be lifesaving in these patients, but managing therapy in an era of progressive antibiotic resistance has become a real issue. This review discusses the challenges faced when treating severe infections in these high-risk patients. PMID:25939918

  10. Emergency department antimicrobial considerations in severe sepsis.

    PubMed

    Green, Robert S; Gorman, Sean K

    2014-11-01

    Severe sepsis and septic shock are common problems in the emergency department patient population and require expert clinical skill by members of the emergency department team to maximize optimal patient outcomes. Although various guidelines have been developed for the management of these patients, issues around antimicrobial-related considerations in critically ill patients require further evidence-based attention. In this review article, important factors related to patient illness, microorganism, timing of antimicrobial administration, and source control are discussed. PMID:25441038

  11. THE EPITHELIUM AS A TARGET IN SEPSIS.

    PubMed

    Chawla, Lakhmir S; Fink, Mitchell; Goldstein, Stuart L; Opal, Steven; Gómez, Alonso; Murray, Patrick; Gómez, Hernando; Kellum, John A

    2016-03-01

    Organ dysfunction induced by sepsis has been consistently associated with worse outcome and death. Regardless of the organ compromised, epithelial dysfunction is present throughout the body, affecting those organs that contain epithelia like the skin, lungs, liver, gut, and kidneys. Despite their obvious differences, sepsis seems to alter common features of all epithelia, such as barrier function and vectorial ion transport. Such alterations in the lung, the gut, and the kidney have direct implications that may explain the profound organ functional impairments in the absence of overt cell death. Epithelial injury in this context is not only an explanatory real pathophysiologic event, but also represents a source of biomarkers that have been explored to identify organ compromise earlier, predict outcome, and even to test novel therapeutic interventions such as blood purification. However, this remains largely experimental, and despite promising results, work is still required to better understand the response of the epithelial cells to sepsis, to define their role in adaptation to insults, to comprehend the interorgan cross-talk that occurs in these circumstances, and to exploit these aspects in pursuit of targeted therapies like blood purification, which may improve outcome for these patients in the future. PMID:26863125

  12. Reduction in maternal mortality due to sepsis.

    PubMed

    Chhabra, S; Kaipa, A; Kakani, A

    2005-02-01

    The present study was undertaken at a rural medical institute in India to analyse the trends in maternal mortality due to sepsis and the factors associated with change, if any. During the study period of 20 years, a total of 37,155 women delivered, 192 deaths occurred and forty deaths (20.83%) were due to sepsis and it's sequlae. It was revealed that there is a definite decrease in the proportion of deaths due to sepsis, to 10% in the last five years from 35% in earlier years. The change seems to be due to the advocacy of clean deliveries and reduction in case fatality because of alterations in medication and earlier surgical intervention. However the percentage contribution of septic abortion has remained the same. Septic abortion continues to exist inspite of all the current laws and discussion about the availability of a liberal law, which permits abortion almost on request. Most of the women who had died due to septic abortion were married (65%). Deaths due to septic abortion, are persisting even in married women and it is a matter of concern for health providers, policy makers and governments. PMID:15814392

  13. A Study of Sepsis in Surgical Wounds

    PubMed Central

    Hnatko, S. I.; Macdonald, G. R.; Rodin, A. E.

    1963-01-01

    Published records of the frequency of wound sepsis are often unreliable sources of information on the general frequency of this complication because of unstandardized methods of reporting and because of the various views of different investigators as to what constitutes sepsis. A method of infection reporting, its study and analysis are outlined. A survey of postoperative infections by this method for the years 1959, 1960 and 1961 revealed infection rates of 2.02%, 1.20% and 1.14%, respectively. For the same period the percentages of wound infections caused by Staph. aureus were 83.06%, 69.8% and 51.8%, respectively. The most prevalent phage types were 55/53/54 and 52/80/81/82, although types 80/81/82 and 80 were also involved. Infections with Gram-negative organisms were encountered more often in 1961 than in 1959. The majority of these were of mixed type, and followed abdominal surgery. There is need for more comprehensive study and analysis of postoperative wound sepsis and its complications. It was apparent from this study that, statistically, a relatively low rate of postoperative infections may mask a high rate following a specific surgical procedure. PMID:13954844

  14. 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

  15. Evaluation of Limb-Girdle Muscular Dystrophy

    ClinicalTrials.gov

    2014-03-06

    Becker Muscular Dystrophy; Limb-Girdle Muscular Dystrophy, Type 2A (Calpain-3 Deficiency); Limb-Girdle Muscular Dystrophy, Type 2B (Miyoshi Myopathy, Dysferlin Deficiency); Limb-Girdle Muscular Dystrophy, Type 2I (FKRP-deficiency)

  16. [Prevention and treatment strategy for burn wound sepsis in children].

    PubMed

    Niu, Xihua; Li, Xiaoling

    2016-02-01

    Wound sepsis is one of the main causes of death in patients with severe burn and trauma. The high incidence of burn wound sepsis in children is attributed to their imperfect immune system function, poor resistance against infection, and the weakened skin barrier function after burn. The key to reduce the mortality of pediatric patients with burn wound sepsis is to enhance the understanding of its etiology, epidemiology, pathogenesis, and diagnostic criteria, in order to improve its early diagnosis and treatment. PMID:26902271

  17. Recognizing and managing sepsis: what needs to be done?

    PubMed

    Yealy, Donald M; Huang, David T; Delaney, Anthony; Knight, Marian; Randolph, Adrienne G; Daniels, Ron; Nutbeam, Tim

    2015-01-01

    Sepsis is associated with significant morbidity and mortality if not promptly recognized and treated. Since the development of early goal-directed therapy, mortality rates have decreased, but sepsis remains a major cause of death in patients arriving at the emergency department or staying in hospital. In this forum article, we asked clinicians and researchers with expertise in sepsis care to discuss the importance of rapid detection and treatment of the condition, as well as special considerations in different patient groups. PMID:25927426

  18. Inhibition of Intestinal Thiamin Transport in Rat Model of Sepsis

    PubMed Central

    Sassoon, Catherine S.; Zhu, Ercheng; Fang, Liwei; Subramanian, Veedamali S.; Said, Hamid M.

    2016-01-01

    Objective Thiamin deficiency is highly prevalent in patients with sepsis, but the mechanism by which sepsis induces thiamin deficiency is unknown. This study aimed to determine the influence of various severity of sepsis on carrier-mediated intestinal thiamin uptake, level of expressions of thiamin transporters (thiamin transporter-1 (THTR-1) and thiamin transporter-2 (THTR-2)), and mitochondrial thiamin pyrophosphate transporter (MTPPT). Design Randomized, controlled study Setting Research laboratory at a Veterans Affairs Medical Center Subjects Twenty-four Sprague-Dawley rats were randomized into controls, mild, moderate and severe sepsis with equal number of animals in each group. Measurements and Main Results Sepsis was induced by cecal ligation and puncture with the cecum ligated below the cecal valve at 25 %, 50 % and 75 % of cecal length, defined as severe, moderate and mild sepsis, respectively. Control animals underwent laparotomy only. After 2 days of induced sepsis, carrier-mediated intestinal thiamin uptake was measured using [3H]thiamin. Expressions of THTR-1, THTR-2, and MTPPT proteins and mRNA were measured. Proinflammatory cytokines (IL-1β and IL-6), and adenosine triphosphate (ATP) were also measured. Sepsis inhibited [3H]thiamin uptake and the inhibition was a function of sepsis severity. Both cell membranes thiamin transporters and MTPPT expression levels were suppressed; also levels of ATP in the intestine of animals with moderate and severe sepsis were significantly lower than that of sham operated controls. Conclusions For the first time we demonstrated that sepsis inhibited carrier-mediated intestinal thiamin uptake as a function of sepsis severity, suppressed thiamin transporters and MTPPT, leading to ATP depletion. PMID:27065466

  19. 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

  20. Experimental treatments for mitochondrial dysfunction in sepsis: A narrative review

    PubMed Central

    Zheng, Guilang; Lyu, Juanjuan; Huang, Jingda; Xiang, Dan; Xie, Meiyan; Zeng, Qiyi

    2015-01-01

    Sepsis is a systemic inflammatory response to infection. Sepsis, which can lead to severe sepsis, septic shock, and multiple organ dysfunction syndrome, is an important cause of mortality. Pathogenesis is extremely complex. In recent years, cell hypoxia caused by mitochondrial dysfunction has become a hot research field. Sepsis damages the structure and function of mitochondria, conversely, mitochondrial dysfunction aggravated sepsis. The treatment of sepsis lacks effective specific drugs. The aim of this paper is to undertake a narrative review of the current experimental treatment for mitochondrial dysfunction in sepsis. The search was conducted in PubMed databases and Web of Science databases from 1950 to January 2014. A total of 1,090 references were retrieved by the search, of which 121 researches met all the inclusion criteria were included. Articles on the relationship between sepsis and mitochondria, and drugs used for mitochondrial dysfunction in sepsis were reviewed retrospectively. The drugs were divided into four categories: (1) Drug related to mitochondrial matrix and respiratory chain, (2) drugs of mitochondrial antioxidant and free radical scavengers, (3) drugs related to mitochondrial membrane stability, (4) hormone therapy for septic mitochondria. In animal experiments, many drugs show good results. However, clinical research lacks. In future studies, the urgent need is to develop promising drugs in clinical trials. PMID:25983774

  1. 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

  2. Biology and Metabolism of Sepsis: Innate Immunity, Bioenergetics, and Autophagy.

    PubMed

    Lewis, Anthony J; Billiar, Timothy R; Rosengart, Matthew R

    2016-06-01

    Sepsis is a complex, heterogeneous physiologic condition that represents a significant public health concern. While many insights into the pathophysiology of sepsis have been elucidated over the past decades of research, important questions remain. This article serves as a review of several important areas in sepsis research. Understanding the innate immune response has been at the forefront as of late, especially in the context of cytokine-directed therapeutic trials. Cellular bioenergetic changes provide insight into the development of organ dysfunction in sepsis. Autophagy and mitophagy perform crucial cell housekeeping and stress response functions. Finally, age-related changes and their potential impact on the septic response are reviewed. PMID:27093228

  3. 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

  4. Ecthyma gangrenosum: an important feature of pseudomonal sepsis in a previously well child.

    PubMed

    Goolamali, S I; Fogo, A; Killian, L; Shaikh, H; Brathwaite, N; Ford-Adams, M; Macfarlane, S

    2009-07-01

    Ecthyma gangrenosum is a rare, distinctive skin disorder associated with potentially fatal underlying pseudomonal sepsis. Although typically occurring in neutropenic or immunocompromised patients, it can occasionally affect healthy children. The appearances are characteristic with small indurated vesicular papules progressing rapidly to infarcted necrotic areas with surrounding erythema and a typical black eschar. In young children, these are often accompanied by fever and diarrhoea. The absence of suppuration and slough distinguishes it from the more recognized pyoderma gangrenosum. Lesions can occur at any site although are most commonly found over the buttocks, limbs, axillae and perineum. We describe the case of a 28-month-old, previously well child who presented with typical features of ecthyma gangrenosum secondary to Pseudomonas infection who responded to appropriate antibiotic treatment. Despite a thorough search, no underlying cause was found. Early recognition and prompt treatment with antipseudomonal antibiotics is vital to reduce morbidity and potential mortality. PMID:19094136

  5. Different regulation of Toll-like receptor 4 expression on blood CD14+ monocytes by simvastatin in patients with sepsis and severe sepsis

    PubMed Central

    Shao, Huanzhang; Wang, Cunzhen; Zhu, Wenliang; Huang, Xiaopei; Guo, Zhisong; Zhang, Huifeng; Qin, Bingyu

    2015-01-01

    We have demonstrated that regulation of Toll-like receptor 4 (TLR4) surface expression levels on blood CD14+ monocytes by simvastatin treatment in patient with sepsis is different from that in patients with severe sepsis. In patients with sepsis simvastatin treatment statistically significantly decreased TLR4 surface expression level on blood CD14+ monocytes, while in patients with severe sepsis simvastatin treatment had no significant influence on TLR4 surface expression level on blood CD14+ monocytes. The changes of plasma interleukin-6 (IL-6) induced by simvastatin in patients with sepsis and severe sepsis were similar with that of TLR4. Our results indicated simvastatin treatment differently influenced inflammation process in patients with sepsis and severe sepsis, which might partially explain the discrepancy, presented by previous trials, about the therapeutic effects of simvastatin treatment in patients with sepsis and severe sepsis. PMID:26550333

  6. PRECICE intramedullary limb lengthening system.

    PubMed

    Paley, Dror

    2015-05-01

    The PRECICE(®) Intramedullary Limb Lengthening System (Ellipse Technologies Inc., CA, USA) is a remotely controlled, magnetically driven, implantable limb lengthening intramedullary nail system. It has both CE mark and US FDA clearance for its first- (2011) and second-generation (2013) implants. It is indicated for the treatment of limb length discrepancy and short stature. It has been used worldwide in over 1000 cases. Its reported and published results in over 250 cases has been excellent with less pain and lower complication rates than with external fixation methods or previous implantable nail systems. PMID:25692375

  7. Management of Major Limb Injuries

    PubMed Central

    Langer, Vijay

    2014-01-01

    Management of major limb injuries is a daunting challenge, especially as many of these patients have severe associated injuries. In trying to save life, often the limb is sacrificed. The existing guidelines on managing such trauma are often confusing. There is scope to lay down such protocols along with the need for urgent transfer of such patients to a multispecialty center equipped to salvage life and limb for maximizing outcome. This review article comprehensively deals with the issue of managing such major injuries. PMID:24511296

  8. Phantom limbs and neural plasticity.

    PubMed

    Ramachandran, V S; Rogers-Ramachandran, D

    2000-03-01

    The study of phantom limbs has received tremendous impetus from recent studies linking changes in cortical topography with perceptual experience. Systematic psychophysical testing and functional imaging studies on patients with phantom limbs provide 2 unique opportunities. First, they allow us to demonstrate neural plasticity in the adult human brain. Second, by tracking perceptual changes (such as referred sensations) and changes in cortical topography in individual patients, we can begin to explore how the activity of sensory maps gives rise to conscious experience. Finally, phantom limbs also allow us to explore intersensory effects and the manner in which the brain constructs and updates a "body image" throughout life. PMID:10714655

  9. Prevalence and Characteristics of Phantom Limb Pain and Residual Limb Pain in the Long Term after Upper Limb Amputation

    ERIC Educational Resources Information Center

    Desmond, Deirdre M.; MacLachlan, Malcolm

    2010-01-01

    This study aims to describe the prevalence and characteristics of phantom limb pain and residual limb pain after upper limb amputation. One-hundred and forty-one participants (139 males; mean age 74.8 years; mean time since amputation 50.1 years) completed a self-report questionnaire assessing residual and phantom limb pain experience. Prevalence…

  10. Limb and hemispatial hypometria.

    PubMed

    Meador, K J; Moore, E E; Martin, R C; Loring, D W; Hess, D C; Heilman, K M

    2000-01-01

    In a previous study, we demonstrated that unilateral cerebral lesions produce hypometric limb movements of the contralateral arm and hemispatial (i.e., directional) hypometria for movements towards contralateral hemispace. In the present study, we investigated 10 patients with right cerebral lesions and 25 healthy controls using a task to uncouple deficits in sensory perceptual systems and motor-action output systems on directional hypometria. This task required participants, with their eyes closed, to reproduce lateral and medial horizontal displacements (15-27 cm) with each arm. Each participant was seated at a waist high table and had their hand placed at an origin point aligned with the axillary fold on the same side. Their hand was moved by the investigator from the origin point to a target point and brought back to the point of origin (input displacement). The participant was then asked to return their hand to either the same target point or to an equidistant target point in the opposite direction. Healthy dextral participants were significantly more hypometric with their right arm, but patients with right cerebral lesions exhibited an opposite pattern with overall left arm hypometria. In addition, patients were significantly more hypometric for movements when output displacements were toward left hemispace. No effect was found for direction of sensory input. The results suggest that the directional hypometria is predominantly produced by hemispatial output deficits. PMID:10761369

  11. Designing a Pediatric Severe Sepsis Screening Tool

    PubMed Central

    Sepanski, Robert J.; Godambe, Sandip A.; Mangum, Christopher D.; Bovat, Christine S.; Zaritsky, Arno L.; Shah, Samir H.

    2014-01-01

    We sought to create a screening tool with improved predictive value for pediatric severe sepsis (SS) and septic shock that can be incorporated into the electronic medical record and actively screen all patients arriving at a pediatric emergency department (ED). “Gold standard” SS cases were identified using a combination of coded discharge diagnosis and physician chart review from 7,402 children who visited a pediatric ED over 2 months. The tool’s identification of SS was initially based on International Consensus Conference on Pediatric Sepsis (ICCPS) parameters that were refined by an iterative, virtual process that allowed us to propose successive changes in sepsis detection parameters in order to optimize the tool’s predictive value based on receiver operating characteristics (ROC). Age-specific normal and abnormal values for heart rate (HR) and respiratory rate (RR) were empirically derived from 143,603 children seen in a second pediatric ED over 3 years. Univariate analyses were performed for each measure in the tool to assess its association with SS and to characterize it as an “early” or “late” indicator of SS. A split-sample was used to validate the final, optimized tool. The final tool incorporated age-specific thresholds for abnormal HR and RR and employed a linear temperature correction for each category. The final tool’s positive predictive value was 48.7%, a significant, nearly threefold improvement over the original ICCPS tool. False positive systemic inflammatory response syndrome identifications were nearly sixfold lower. PMID:24982852

  12. Why study human limb malformations?

    PubMed Central

    Wilkie, Andrew OM

    2003-01-01

    Congenital limb malformations occur in 1 in 500 to 1 in 1000 human live births and include both gross reduction defects and more subtle alterations in the number, length and anatomy of the digits. The major causes of limb malformations are abnormal genetic programming and intra-uterine disruption to development. The identification of causative gene mutations is important for genetic counselling and also provides insights into the mechanisms controlling limb development. This article illustrates some of the lessons learnt from the study of human limb malformation, organized into seven categories. These are: (1) identification of novel genes, (2) allelic mutation series, (3) pleiotropy, (4) qualitative or (5) quantitative differences between mouse and human development, (6) physical and teratogenic disruption, and (7) unusual biological phenomena. PMID:12587917

  13. Administration of bone marrow stromal cells in sepsis attenuates sepsis-related coagulopathy.

    PubMed

    Tan, Lifei; Huang, Yueyue; Pan, Xiaojun; Quan, Shichao; Xu, Shunyao; Li, Dequan; Song, Lijun; Zhang, Xiaomin; Chen, Wanzhou; Pan, Jingye

    2016-06-01

    Introduction Coagulopathy plays an important role in sepsis. The aim of this study was to determine whether bone marrow stromal cell (BMSC) administration could attenuate coagulopathy in sepsis. Materials and methods In vitro: endothelial cells were cultured with/without BMSCs for 6 h following LPS stimulation and were collected for thrombomodulin (TM) and endothelial protein C receptor (EPCR) measurements. In vivo: Thirty-six mice were randomized into sham, sepsis, and sepsis + BMSC groups (n = 12 each group). Sepsis was induced through cecal ligation and puncture (CLP). BMSC infusion was started at 6 h after CLP. Lung tissues and plasma samples were collected at 24 h after CLP for enzyme-linked immunosorbent assay (ELISA), quantitative real-time RT-PCR, western blot, and immunohistochemistry analysis. Results In vitro: BMSCs attenuated the decrease in TM and EPCR mRNA and protein expression levels in LPS-stimulated endothelial cells. In vivo: BMSC treatment decreased lung injury and mesenteric perfusion impairment, and ameliorated coagulopathy, as suggested by the reduction in elevated TF, vWF, and TAT circulation levels. BMSC infusion decreased TF mRNA transcription and protein expression levels in lung tissues, and increased TM and EPCR mRNA transcription and expression levels. Discussion BMSC administration attenuated coagulopathy, and decreased lung injury and mesenteric perfusion impairment in sepsis. Key messages BMSCs increased the expression of TM and EPCR from endothelium cells exposed to LPS in vitro. BMSC treatment attenuated lung injury and coagulopathy in the mice cecal ligation and puncture (CLP) model. BMSC administration-attenuated coagulopathy is related to the reduced expression of TF and increased expression of TM and EPCR. PMID:26969493

  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. Improving the management and care of people with sepsis.

    PubMed

    Fitzpatrick, David; McKenna, Michael; Rooney, Kevin; Beckett, Dan; Pringle, Norma

    2014-04-01

    Many hospitals struggle to implement the full sepsis care bundle, but research suggests that many patients with sepsis are transported to hospital by ambulance. In 2011, the Scottish Ambulance Service introduced a pre-hospital sepsis screening tool (PSST) to expedite sepsis identification and care delivery. However, ambulance clinicians have reported varying degrees of interest and enthusiasm from hospital staff during handover. Therefore, an online survey was set up to investigate medical and nursing staff perceptions and experiences of the introduction of a PSST. This article discusses the results, which show that participants perceive the PSST reduces time to treatment, improves continuity of care, benefits patients and is accurately applied by ambulance clinicians, but which also highlight problems with communication. The delivery of in-hospital and pre-hospital sepsis care is challenging, but simple measures such as improving and standardising communication and alert systems between ambulance services and receiving hospitals could improve the clinical effects of a PSST. PMID:24689480

  16. Sepsis in Old Age: Review of Human and Animal Studies

    PubMed Central

    Starr, Marlene E; Saito, Hiroshi

    2014-01-01

    Sepsis is a serious problem among the geriatric population as its incidence and mortality rates dramatically increase with advanced age. Despite a large number of ongoing clinical and basic research studies, there is currently no effective therapeutic strategy that rescues elderly patients with severe sepsis. Recognition of this problem is relatively low as compared to other age-associated diseases. The disparity between clinical and basic studies is a problem, and this is likely due, in part, to the fact that most laboratory animals used for sepsis research are not old while the majority of sepsis cases occur in the geriatric population. The objective of this article is to review recent epidemiological studies and clinical observations, and compare these with findings from basic laboratory studies which have used aged animals in experimental sepsis. PMID:24729938

  17. 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

  18. 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

  19. 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

  20. Sepsis-associated AKI: epithelial cell dysfunction.

    PubMed

    Emlet, David R; Shaw, Andrew D; Kellum, John A

    2015-01-01

    Acute kidney injury (AKI) occurs frequently in critically ill patients with sepsis, in whom it doubles the mortality rate and half of the survivors suffer permanent kidney damage or chronic kidney disease. Failure in the development of viable therapies has prompted studies to better elucidate the cellular and molecular etiologies of AKI, which have generated novel theories and paradigms for the mechanisms of this disease. These studies have shown multifaceted origins and elements of AKI that, in addition to/in lieu of ischemia, include the generation of damage-associated molecular patterns and pathogen-associated molecular patterns, the inflammatory response, humoral and cellular immune activation, perturbation of microvascular flow and oxidative stress, bioenergetic alterations, cell-cycle alterations, and cellular de-differentiation/re-differentiation. It is becoming clear that a major etiologic effector of all these inputs is the renal tubule epithelial cell (RTEC). This review discusses these elements and their effects on RTECs, and reviews the current hypotheses of how these effects may determine the fate of RTECs during sepsis-induced AKI. PMID:25795502

  1. Lactoferrin for prevention of neonatal sepsis

    PubMed Central

    Turin, Christie G.; Zea-Vera, Alonso; Pezo, Alonso; Cruz, Karen; Zegarra, Jaime; Bellomo, Sicilia; Cam, Luis; Llanos, Raul; Castañeda, Anne; Tucto, Lourdes; Ochoa, Theresa J.

    2015-01-01

    Preterm neonates are at risk to acquire infections. In addition to the high mortality associated with sepsis, these patients are at risk for long-term disabilities, particularly neurodevelopment impairment. Several interventions have been evaluated to reduce rates of infections in neonates but have not proven efficacy. Lactoferrin (LF), a milk glycoprotein with anti-inflammatory, immunomodulatory and anti-microbial properties, has the potential to prevent infections in young children. We performed a review of current and ongoing clinical trials of LF for prevention of neonatal sepsis, and found eleven registered clinical trials that include more than 6000 subjects. Few of these trials have finished; despite their small sample size, the preliminary results show a trend towards a positive protective effect of LF on neonatal infections. Larger trials are underway to confirm the findings of these initial studies. This information will help to define LF´s role in clinical settings and, if proven effective, would profoundly affect the treatment of low birth weight neonates as a cost-effective intervention worldwide. PMID:24935001

  2. Intestinal radiation syndrome: sepsis and endotoxin

    SciTech Connect

    Geraci, J.P.; Jackson, K.L.; Mariano, M.S.

    1985-03-01

    Rats were whole-body irradiated with 8-MeV cyclotron-produced neutrons and /sup 137/Cs ..gamma.. rays to study the role of enteric bacteria and endotoxin in the intestinal radiation syndrome. Decrease in intestinal weight was used as an index of radiation-induced breakdown of the mucosa. Neutron and ..gamma..-ray doses that were sublethal for intestinal death resulted in a dose-dependent decrease in intestinal weight, reaching minimal values 2 to 3 days after exposure, followed by recovery within 5 days after irradiation. Neutron and photon doses that caused intestinal death resulted in greater mucosal breakdown with little or no evidence of mucosal recovery. The presence of fluid in the intestine and diarrhea, but not bacteremia or endotoxemia, were related to mucosal breakdown and recovery. Neither sepsis nor endotoxin could be detected in liver samples taken at autopsy from animals which died a short time earlier from intestinal injury. These results suggest that overt sepsis and endotoxemia do not play a significant role in the intestinal radiation syndrome.

  3. Isolated Limb Infusion for Limb Salvage in Limb Threatening Extremity Sarcomas

    PubMed Central

    Vohra, Nasreen A.; Turaga, Kiran K.; Gonzalez, Ricardo J.; Conley, Anthony; Reed, Damon; Bui, Marilyn M.; Cheong, David; Letson, Douglas G.; Zager, Jonathan S.

    2015-01-01

    Background Locally advanced, limb threatening soft tissue sarcomas (STS) pose a significant treatment challenge. We report our experience using isolated limb infusion (ILI) in patients with unresectable extremity STS. Methods Twenty-two patients with extremity STS underwent 26 ILIs with melphalan and dactinomycin. Patient characteristics, intra-operative parameters and toxicity were recorded. Outcome measures included limb-salvage and in-field response rates. Results Of the 19 lower and 7 upper extremity ILIs, Wieberdink grade III toxicity or less was observed in all. Median follow up was 11 months. Seventeen patients were evaluable at 3 months post ILI with an overall response rate of 42%. Four (24%) had complete response (CR), 3 (18%) partial response (PR), 3 (18%) stable disease (SD) and 7 (41%) progressive disease (PD). Twelve of 17 (71%) underwent successful limb preservation at a median of 9 months post ILI. Two (12%) were downstaged to resectable disease and remain NED after surgery at 30 and 22 months post ILI. Conclusions ILI is an attractive modality that provides regional disease control and limb preservation in patients with limb threatening sarcoma. Although short term results appear encouraging, long term follow up is needed to fully assess the role of ILI in unresectable extremity STS. PMID:23205633

  4. The phantom limb in dreams.

    PubMed

    Brugger, Peter

    2008-12-01

    Mulder and colleagues [Mulder, T., Hochstenbach, J., Dijkstra, P. U., Geertzen, J. H. B. (2008). Born to adapt, but not in your dreams. Consciousness and Cognition, 17, 1266-1271.] report that a majority of amputees continue to experience a normally-limbed body during their night dreams. They interprete this observation as a failure of the body schema to adapt to the new body shape. The present note does not question this interpretation, but points to the already existing literature on the phenomenology of the phantom limb in dreams. A summary of published investigations is complemented by a note on phantom phenomena in the dreams of paraplegic patients and persons born without a limb. Integration of the available data allows the recommendation for prospective studies to consider dream content in more detail. For instance, "adaptation" to the loss of a limb can also manifest itself by seeing oneself surrounded by amputees. Such projective types of anosognosia ("transitivism") in nocturnal dreams should also be experimentally induced in normally-limbed individuals, and some relevant techniques are mentioned. PMID:18313942

  5. Challenges in the diagnosis and management of neonatal sepsis

    PubMed Central

    Zea-Vera, Alonso

    2015-01-01

    Neonatal sepsis is the third leading cause of neonatal mortality and a major public health problem, especially in developing countries. Although recent medical advances have improved neonatal care, many challenges remain in the diagnosis and management of neonatal infections. The diagnosis of neonatal sepsis is complicated by the frequent presence of noninfectious conditions that resemble sepsis, especially in preterm infants, and by the absence of optimal diagnostic tests. Since neonatal sepsis is a high-risk disease, especially in preterm infants, clinicians are compelled to empirically administer antibiotics to infants with risk factors and/or signs of suspected sepsis. Unfortunately, both broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are associated with adverse outcomes and increase antimicrobial resistance rates. Given the high incidence and mortality of sepsis in preterm infants and its long-term consequences on growth and development, efforts to reduce the rates of infection in this vulnerable population are one of the most important interventions in neonatal care. In this review, we discuss the most common questions and challenges in the diagnosis and management of neonatal sepsis, with a focus on developing countries. PMID:25604489

  6. Toward an operative diagnosis in sepsis: a latent class approach

    PubMed Central

    De La Rosa, Gisela D; Valencia, Marta L; Arango, Clara M; Gomez, Carlos I; Garcia, Alex; Ospina, Sigifredo; Osorno, Susana; Henao, Adriana; Jaimes, Fabián A

    2008-01-01

    Background Recent data have suggested that 18 million of new sepsis cases occur each year worldwide, with a mortality rate of almost 30%. There is not consensus on the clinical definition of sepsis and, because of lack of training or simply unawareness, clinicians often miss or delay this diagnosis. This is especially worrying; since there is strong evidence supporting that early treatment is associated with greater clinical success. There are some difficulties for sepsis diagnosis such as the lack of an appropriate gold standard to identify this clinical condition. This situation has hampered the assessment of the accuracy of clinical signs and biomarkers to diagnose sepsis. Methods/design Cross-sectional study to determine the operative characteristics of three biological markers of inflammation and coagulation (D-dimer, C-reactive protein and Procalcitonin) as diagnostic tests for sepsis, in patients admitted to hospital care with a presumptive infection as main diagnosis. Discussion There are alternative techniques that have been used to assess the accuracy of tests without gold standards, and they have been widely used in clinical disciplines such as psychiatry, even though they have not been tested in sepsis diagnosis. Considering the main importance of diagnosis as early as possible, we propose a latent class analysis to evaluate the accuracy of three biomarkers to diagnose sepsis. PMID:18284667

  7. Brain microabscesses in a porcine model of Staphylococcus aureus sepsis

    PubMed Central

    2013-01-01

    Background Sepsis caused by Staphylococcus aureus often leads to brain microabscesses in humans. Animal models of haematogenous brain abscesses would be useful to study this condition in detail. Recently, we developed a model of S. aureus sepsis in pigs and here we report that brain microabscesses develop in pigs with such induced S. aureus sepsis. Twelve pigs were divided into three groups. Nine pigs received an intravenous inoculation of S. aureus once at time 0 h (group 1) or twice at time 0 h and 12 h (groups 2 and 3). In each group the fourth pig served as control. The pigs were euthanized at time 12 h (Group 1), 24 h (Group 2) and 48 h (Group 3) after the first inoculation. The brains were collected and examined histopathologically. Results All inoculated pigs developed sepsis and seven out of nine pigs developed brain microabscesses. The microabscesses contained S. aureus and were located in the prosencephalon and mesencephalon. Chorioditis and meningitis occurred from 12 h after inoculation. Conclusions Pigs with experimental S. aureus sepsis often develop brain microabscesses. The porcine brain pathology mirrors the findings in human sepsis patients. We therefore suggest the pig as a useful animal model of the development of brain microabscesses caused by S. aureus sepsis. PMID:24176029

  8. Proteomic and epigenomic markers of sepsis-induced delirium (SID)

    PubMed Central

    Sfera, Adonis; Price, Amy I.; Gradini, Roberto; Cummings, Michael; Osorio, Carolina

    2015-01-01

    In elderly population sepsis is one of the leading causes of intensive care unit (ICU) admissions in the United States. Sepsis-induced delirium (SID) is the most frequent cause of delirium in ICU (Martin et al., 2010). Together delirium and SID represent under-recognized public health problems which place an increasing financial burden on the US health care system, currently estimated at 143–152 billion dollars per year (Leslie et al., 2008). The interest in SID was recently reignited as it was demonstrated that, contrary to prior beliefs, cognitive deficits induced by this condition may be irreversible and lead to dementia (Pandharipande et al., 2013; Brummel et al., 2014). Conversely, it is construed that diagnosing SID early or mitigating its full blown manifestations may preempt geriatric cognitive disorders. Biological markers specific for sepsis and SID would facilitate the development of potential therapies, monitor the disease process and at the same time enable elderly individuals to make better informed decisions regarding surgeries which may pose the risk of complications, including sepsis and delirium. This article proposes a battery of peripheral blood markers to be used for diagnostic and prognostic purposes in sepsis and SID. Though each individual marker may not be specific enough, we believe that together as a battery they may achieve the necessary accuracy to answer two important questions: who may be vulnerable to the development of sepsis, and who may develop SID and irreversible cognitive deficits following sepsis? PMID:26579527

  9. Proteomic and epigenomic markers of sepsis-induced delirium (SID).

    PubMed

    Sfera, Adonis; Price, Amy I; Gradini, Roberto; Cummings, Michael; Osorio, Carolina

    2015-01-01

    In elderly population sepsis is one of the leading causes of intensive care unit (ICU) admissions in the United States. Sepsis-induced delirium (SID) is the most frequent cause of delirium in ICU (Martin et al., 2010). Together delirium and SID represent under-recognized public health problems which place an increasing financial burden on the US health care system, currently estimated at 143-152 billion dollars per year (Leslie et al., 2008). The interest in SID was recently reignited as it was demonstrated that, contrary to prior beliefs, cognitive deficits induced by this condition may be irreversible and lead to dementia (Pandharipande et al., 2013; Brummel et al., 2014). Conversely, it is construed that diagnosing SID early or mitigating its full blown manifestations may preempt geriatric cognitive disorders. Biological markers specific for sepsis and SID would facilitate the development of potential therapies, monitor the disease process and at the same time enable elderly individuals to make better informed decisions regarding surgeries which may pose the risk of complications, including sepsis and delirium. This article proposes a battery of peripheral blood markers to be used for diagnostic and prognostic purposes in sepsis and SID. Though each individual marker may not be specific enough, we believe that together as a battery they may achieve the necessary accuracy to answer two important questions: who may be vulnerable to the development of sepsis, and who may develop SID and irreversible cognitive deficits following sepsis? PMID:26579527

  10. Mortality in Sepsis and its relationship with Gender

    PubMed Central

    Nasir, Nosheen; Jamil, Bushra; Siddiqui, Shahla; Talat, Najeeha; Khan, Fauzia A.; Hussain, Rabia

    2015-01-01

    Background and Objective: Sepsis remains a leading cause of death across the world, carrying a mortality rate of 20–50%. Women have been reported to be less likely to suffer from sepsis and to have a lower risk of mortality from sepsis compared to men. The objective of this study was to determine the relationship between gender and mortality in sepsis, and compare cytokine profiles of male and female patients. Methods: This was a prospective case series on 97 patients admitted with sepsis. Clinical and microbiological data was gathered, blood samples were collected for cytokine (IL-10, IL-6 and TNFα) levels and patients were followed up for clinical outcome. Results: There were 54% males and 46% females, with no significant difference of age or comorbids between genders. Respiratory tract infection was the commonest source of sepsis, and was more common in females (60%) compared to males (39%) (p=0.034). Males had a higher mortality (p=0.048, RR 1.73) and plasma IL-6 level(p=0.040) compared to females. Mean IL-6 plasma level was significantly (p<0.01) higher in patients who died vs. who recovered. Conclusion: Our study shows that males with sepsis have a 70% greater mortality rate, and mortality is associated with a higher IL-6 plasma level. PMID:26649014

  11. Choice of Fluid Therapy in the Initial Management of Sepsis, Severe Sepsis, and Septic Shock.

    PubMed

    Chang, Ronald; Holcomb, John B

    2016-07-01

    Sepsis results in disruption of the endothelial glycocalyx layer and damage to the microvasculature, resulting in interstitial accumulation of fluid and subsequently edema. Fluid resuscitation is a mainstay in the initial treatment of sepsis, but the choice of fluid is unclear. The ideal resuscitative fluid is one that restores intravascular volume while minimizing edema; unfortunately, edema and edema-related complications are common consequences of current resuscitation strategies. Crystalloids are recommended as first-line therapy, but the type of crystalloid is not specified. There is increasing evidence that normal saline is associated with increased mortality and kidney injury; balanced crystalloids may be a safer alternative. Albumin is similar to crystalloids in terms of outcomes in the septic population but is costlier. Hydroxyethyl starches appear to increase mortality and kidney injury in the critically ill and are no longer indicated in these patients. In the trauma population, the shift to plasma-based resuscitation with decreased use of crystalloid and colloid in the treatment of hemorrhagic shock has led to decreased inflammatory and edema-mediated complications. Studies are needed to determine if these benefits also occur with a similar resuscitation strategy in the setting of sepsis. PMID:26844975

  12. Potential of surface acoustic wave biosensors for early sepsis diagnosis.

    PubMed

    Csete, Marie; Hunt, William D

    2013-08-01

    Early diagnosis of sepsis is a difficult problem for intensivists and new biomarkers for early diagnosis have been difficult to come by. Here we discuss the potential of adapting a technology from the electronics industry, surface acoustic wave (SAW) sensors, for diagnosis of multiple markers of sepsis in real time, using non-invasive assays of exhaled breath condensate. The principles and advantages of the SAW technology are reviewed as well as a proposed plan for adapting this flexible technology to early sepsis detection. PMID:23471596

  13. Challenges with Diagnosing and Managing Sepsis in Older Adults.

    PubMed

    Clifford, Kalin M; Dy-Boarman, Eliza A; Haase, Krystal K; Maxvill, Kristen; Pass, Steven E; Alvarez, Carlos A

    2016-02-01

    Sepsis in older adults has many challenges that affect rate of septic diagnosis, treatment, and monitoring parameters. Numerous age-related changes and comorbidities contribute to increased risk of infections in older adults, but also atypical symptomatology that delays diagnosis. Due to various pharmacokinetic/pharmacodynamic changes in the older adult, medications are absorbed, metabolized, and eliminated at different rates as compared to younger adults, which increases risk of adverse drug reactions due to use of drug therapy needed for sepsis management. This review provides information to aid in diagnosis and offers recommendations for monitoring and treating sepsis in the older adult population. PMID:26687340

  14. Metabolism, Metabolomics, and Nutritional Support of Patients with Sepsis.

    PubMed

    Englert, Joshua A; Rogers, Angela J

    2016-06-01

    Sepsis is characterized by profound changes in systemic and cellular metabolism that disrupt normal metabolic homeostasis. These metabolic changes can serve as biomarkers for disease severity. Lactate, a metabolite of anaerobic metabolism, is the most widely used ICU biomarker and it is incorporated into multiple management algorithms. Technological advances now make broader metabolic profiling possible, with early studies identifying metabolic changes associated with sepsis mortality. Finally, given the marked changes in metabolism in sepsis and the association of worse prognosis in patients with severe metabolic derangements, we summarize the seminal trials conducted to optimize nutrition in the ICU. PMID:27229648

  15. Sepsis in pregnancy and early goal-directed therapy

    PubMed Central

    Joseph, Julie; Sinha, Aneeta; Paech, Michael; Walters, Barry N J

    2009-01-01

    Sepsis is a major cause of serious morbidity and mortality in pregnant women and their babies. Conventional management has evolved over many years. Improved understanding of the underlying pathophysiology and randomized clinical trials have led to recommendations for the formalization and standardization of the management of severe sepsis in non-pregnant patients. Most of these recommendations are applicable to pregnancy. The Surviving Sepsis Campaign and Early Goal Directed Therapy have relevance to the care of pregnant women with serious infection and are reviewed here.

  16. Update on the management of neonatal sepsis in horses.

    PubMed

    Palmer, Jon

    2014-08-01

    Despite advances in neonatal intensive care sepsis, severe sepsis and septic shock remain the biggest killers of neonatal foals. Management of this severe syndrome remains difficult, requiring intensive intervention. Key aspects of management include infection control, hemodynamic support, immunomodulatory interventions, and metabolic/endocrine support. Infection control largely consists of early antimicrobial therapy, plasma transfusions, and local therapy for the infected focus. In cases with severe sepsis or septic shock, hemodynamic support with fluids, vasoactive agents, and respiratory support insuring oxygen delivery to vital organs is important. Nutritional support is important, but close monitoring is needed to avoid hyperglycemia and hypoglycemia. PMID:25016494

  17. Apparatus for determining changes in limb volume

    NASA Technical Reports Server (NTRS)

    Bhagat, P. K.; Wu, V. C. (Inventor)

    1981-01-01

    Measuring apparatus for determining changes in the volume of limbs or other boty extremities by determining the cross-sectional area of such limbs many comprise a transmitter including first and second transducers for positioning on the surface of the limb at a predetermined distance there between, and a receiver including a receiver crystal for positioning on the surface of the limb. The distance between the receiver crystal and the first and second transducers are represented by respective first and second chords of the cross-section of the limb and the predetermined distance between the first and second transducers is represented by a third chord of the limb cross section.

  18. An Immunological Perspective on Neonatal Sepsis.

    PubMed

    Kan, Bernard; Razzaghian, Hamid Reza; Lavoie, Pascal M

    2016-04-01

    Despite concerted international efforts, mortality from neonatal infections remains unacceptably high in some areas of the world, particularly for premature infants. Recent developments in flow cytometry and next-generation sequencing technologies have led to major discoveries over the past few years, providing a more integrated understanding of the developing human immune system in the context of its microbial environment. We review these recent findings, focusing on how in human newborns incomplete maturation of the immune system before a full term of gestation impacts on their vulnerability to infection. We also discuss some of the clinical implications of this research in guiding the design of more-accurate age-adapted diagnostic and preventive strategies for neonatal sepsis. PMID:26993220

  19. Totem and taboo: fluids in sepsis.

    PubMed

    Hilton, Andrew K; Bellomo, Rinaldo

    2011-01-01

    The need for early, rapid, and substantial fluid resuscitation in septic patients has long been an article of faith in the intensive care community, a tribal totem that is taboo to question. The results of a recent multicenter trial in septic children in Africa, published in The New England Journal of Medicine, powerfully challenge the fluid paradigm. The salient aspects of the trial need to be understood and reflected upon. In this commentary, we discuss the background to and findings of the trial and explain why they will likely trigger a re-evaluation of our thinking about fluids in sepsis, a re-evaluation that is already happening in the treatment of acute respiratory distress syndrome and acute kidney injury and in postoperative care. PMID:21672278

  20. Pediatric limb differences and amputations.

    PubMed

    Le, Joan T; Scott-Wyard, Phoebe R

    2015-02-01

    Congenital limb differences are uncommon birth defects that may go undetected even with prenatal screening ultrasound scans and often go undetected until birth. For children with congenital limb differences, a diagnostic evaluation should be done to rule out syndromes involving other organ systems or known associations. The most common etiology of acquired amputation is trauma. Postamputation complications include pain and terminal bony overgrowth. A multidisciplinary approach to management with the child and family can lead to a successful, functional, and fulfilling life. PMID:25479783

  1. In-111 WBC imaging in musculoskeletal sepsis

    SciTech Connect

    Thompson, L.; Ouzounian, T.J.; Webber, M.M.; Amstutz, H.C.

    1984-01-01

    This study evaluated the accuracy and utility of the In-111 labeled WBC imaging in a series of patients who were suspected of having musculoskeletal sepsis. The labeling of the WBCs was patterned after a method previously described, in which the WBCs are labeled with In-111 oxine in plasma. The WBCs from 100 ml of blood are separated and incubated with In-111 oxine complex, and then 500 ..mu..Ci. of the labeled cells were reinjected into the patient. Images of the areas in question were obtained at 24 hrs. In some instances, 48 hour images were also obtained. Images were interpreted using consistent criteria. Forty imaging procedures were done on 39 patients. These included 39 total joint protheses, and 17 other images to evaluate possible osteomyelitis, septic arthritis or deep abscesses. Of these studies, 15 were positive, and 42 negative. The findings were then correlated with operative culture and pathology in 21, aspiration cultures and gram stains in 14, and with clinical findings in the remaining 21. This correlation showed 41 true negatives, 12 true positives, 1 false negative, and 2 false positives. The sensitivity was 92.9% and the specificity was 95.2%l. The false negative occurred in a patient on chronic suppressive antibiotic therapy for an infected total hip replacement. The false positive images occurred in a patient with active rheumatoid arthritis and in a patient imaged one month post operative placement of the prosthesis. These images were very useful in several septic patients who had many possible sites of infection. The authors conclude that In-III imaging is an accurate and useful non-invasive method of evaluating musculoskeletal sepsis.

  2. Sphingosine 1-phosphate and its carrier apolipoprotein M in human sepsis and in Escherichia coli sepsis in baboons.

    PubMed

    Frej, Cecilia; Linder, Adam; Happonen, Kaisa E; Taylor, Fletcher B; Lupu, Florea; Dahlbäck, Björn

    2016-06-01

    Sphingosine 1-phosphate (S1P) is an important regulator of vascular integrity and immune cell migration, carried in plasma by high-density lipoprotein (HDL)-associated apolipoprotein M (apoM) and by albumin. In sepsis, the protein and lipid composition of HDL changes dramatically. The aim of this study was to evaluate changes in S1P and its carrier protein apoM during sepsis. For this purpose, plasma samples from both human sepsis patients and from an experimental Escherichia coli sepsis model in baboons were used. In the human sepsis cohort, previously studied for apoM, plasma demonstrated disease-severity correlated decreased S1P levels, the profile mimicking that of plasma apoM. In the baboons, a similar disease-severity dependent decrease in plasma levels of S1P and apoM was observed. In the lethal E. coli baboon sepsis, S1P decreased already within 6-8 hrs, whereas the apoM decrease was seen later at 12-24 hrs. Gel filtration chromatography of plasma from severe human or baboon sepsis on Superose 6 demonstrated an almost complete loss of S1P and apoM in the HDL fractions. S1P plasma concentrations correlated with the platelet count but not with erythrocytes or white blood cells. The liver mRNA levels of apoM and apoA1 decreased strongly upon sepsis induction and after 12 hr both were almost completely lost. In conclusion, during septic challenge, the plasma levels of S1P drop to very low levels. Moreover, the liver synthesis of apoM decreases severely and the plasma levels of apoM are reduced. Possibly, the decrease in S1P contributes to the decreased endothelial barrier function observed in sepsis. PMID:26990127

  3. A latent class approach for sepsis diagnosis supports use of procalcitonin in the emergency room for diagnosis of severe sepsis

    PubMed Central

    2013-01-01

    Background Given the acknowledged problems in sepsis diagnosis, we use a novel way with the application of the latent class analysis (LCA) to determine the operative characteristics of C-reactive protein (CRP), D-dimer (DD) and Procalcitonin (PCT) as diagnostic tests for sepsis in patients admitted to hospital care with a presumptive infection. Methods Cross-sectional study to determine the diagnostic accuracy of three biological markers against the gold standard of clinical definition of sepsis provided by an expert committee, and also against the likelihood of sepsis according to LCA. Patients were recruited in the emergency room within 24 hours of hospitalization and were follow-up daily until discharge. Results Among 765 patients, the expert committee classified 505 patients (66%) with sepsis, 112 (15%) with infection but without sepsis and 148 (19%) without infection. The best cut-offs points for CRP, DD, and PCT were 7.8 mg/dl, 1616 ng/ml and 0.3 ng/ml, respectively; but, neither sensitivity nor specificity reach 70% for any biomarker. The LCA analysis with the same three tests identified a “cluster” of 187 patients with several characteristics suggesting a more severe condition as well as better microbiological confirmation. Assuming this subset of patients as the new prevalence of sepsis, the ROC curve analysis identified new cut-off points for the tests and suggesting a better discriminatory ability for PCT with a value of 2 ng/ml. Conclusions Under a “classical” definition of sepsis three typical biomarkers (CRP, PCT and DD) are not capable enough to differentiate septic from non-septic patients in the ER. However, a higher level of PCT discriminates a selected group of patients with severe sepsis. PMID:24050481

  4. 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

  5. A plethora of angiopoietin-2 effects during clinical sepsis

    PubMed Central

    2010-01-01

    The interesting study by Davis and colleagues in the current issue of Critical Care expands on the increasingly recognized role of angiopoietins in human sepsis but raises a number of questions, which are discussed in this commentary. The authors describe an association between elevated angiopoietin (ang)-2 levels and impaired vascular reactivity, measured by the partly nitric oxide-dependent finger hyperemic response to forearm vascular occlusion, in patients with sepsis. This suggests that the ang-1/2-Tie2 system is involved in a number of pathophysiologic, phenotypic and perhaps prognostic alterations in human sepsis, on top of the effect on pulmonary endothelial barrier function. The novel inflammatory route may be a target for future therapeutic studies in human sepsis and acute lung injury, including those with activated protein C. PMID:20587077

  6. HDL in sepsis – risk factor and therapeutic approach

    PubMed Central

    Morin, Emily E.; Guo, Ling; Schwendeman, Anna; Li, Xiang-An

    2015-01-01

    High-density lipoprotein (HDL) is a key component of circulating blood and plays essential roles in regulation of vascular endothelial function and immunity. Clinical data demonstrate that HDL levels drop by 40–70% in septic patients, which is associated with a poor prognosis. Experimental studies using Apolipoprotein A-I (ApoAI) null mice showed that HDL deficient mice are susceptible to septic death, and overexpressing ApoAI in mice to increase HDL levels protects against septic death. These clinical and animal studies support our hypothesis that a decrease in HDL level is a risk factor for sepsis, and raising circulating HDL levels may provide an efficient therapy for sepsis. In this review, we discuss the roles of HDL in sepsis and summarize the efforts of using synthetic HDL as a potential therapy for sepsis. PMID:26557091

  7. Development of an e-learning package for sepsis care.

    PubMed

    Davis, Anna; Henderson, James; Langmack, Gill

    Severe sepsis is a major cause of morbidity and mortality in the UK. This article describes the collaborative development and implementation of an interactive online learning package to understand the key role nurses have in recognising and then starting to apply the Sepsis Six care bundle in clinical practice. The e-learning package, developed in a UK teaching hospital, uses a case study approach to address the knowledge that is required to be able to recognise sepsis, to understand the processes that occur and the ongoing care and treatment required. The package is relevant to final-year student nurses, newly registered nurses in preceptorship and other health professionals involved in assessing and treating patients who may be developing sepsis. PMID:27019164

  8. 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

  9. Paradoxical Roles of the Neutrophil in Sepsis: Protective and Deleterious

    PubMed Central

    Sônego, Fabiane; Castanheira, Fernanda Vargas e Silva; Ferreira, Raphael Gomes; Kanashiro, Alexandre; Leite, Caio Abner Vitorino Gonçalves; Nascimento, Daniele Carvalho; Colón, David Fernando; Borges, Vanessa de Fátima; Alves-Filho, José Carlos; Cunha, Fernando Queiróz

    2016-01-01

    Sepsis, an overwhelming inflammatory response syndrome secondary to infection, is one of the costliest and deadliest medical conditions worldwide. Neutrophils are classically considered to be essential players in the host defense against invading pathogens. However, several investigations have shown that impairment of neutrophil migration to the site of infection, also referred to as neutrophil paralysis, occurs during severe sepsis, resulting in an inability of the host to contain and eliminate the infection. On the other hand, the neutrophil antibacterial arsenal contributes to tissue damage and the development of organ dysfunction during sepsis. In this review, we provide an overview of the main events in which neutrophils play a beneficial or deleterious role in the outcome of sepsis. PMID:27199981

  10. Biomarkers for Sepsis: What Is and What Might Be?

    PubMed Central

    Biron, Bethany M.; Ayala, Alfred; Lomas-Neira, Joanne L.

    2015-01-01

    Every year numerous individuals develop the morbid condition of sepsis. Therefore, novel biomarkers that might better inform clinicians treating such patients are sorely needed. Difficulty in identifying such markers is in part due to the complex heterogeneity of sepsis, resulting from the broad and vague definition of this state/condition based on numerous possible clinical signs and symptoms as well as an incomplete understanding of the underlying pathobiology of this complex condition. This review considers some of the attempts that have been made so far, looking at both the pro- and anti-inflammatory response to sepsis, as well as genomic analysis, as sources of potential biomarkers. Irrespective, for functional biomarker(s) of sepsis to successfully translate from the laboratory to a clinical setting, the biomarker must be target specific and sensitive as well as easy to implement/interpret, and be cost effective, such that they can be utilized routinely in patient diagnosis and treatment. PMID:26417200

  11. Neutrophils, nitric oxide, and microvascular permeability in severe sepsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    STUDY OBJECTIVES: Alterations in microvascular permeability are prevalent in patients with sepsis; a recent study reported that patients with septic shock had increased capillary filtration coefficient (Kf), a noninvasive index of microvascular permeability. We aimed to determine whether patients wi...

  12. Learning about Vertebrate Limb Development

    ERIC Educational Resources Information Center

    Liang, Jennifer O.; Noll, Matthew; Olsen, Shayna

    2014-01-01

    We have developed an upper-level undergraduate laboratory exercise that enables students to replicate a key experiment in developmental biology. In this exercise, students have the opportunity to observe live chick embryos and stain the apical ectodermal ridge, a key tissue required for development of the vertebrate limb. Impressively, every…

  13. Maternal and neonatal sepsis caused by Haemophilus influenzae type d.

    PubMed

    Warren, S; Tristram, S; Bradbury, R S

    2010-03-01

    A 29-year-old pregnant woman was admitted to hospital with signs of sepsis and threatened pre-term labour. The premature neonate also showed signs of sepsis. Haemophilus influenzae biotype III was cultured from a midstream urine sample taken from the mother, maternal placental swabs and neonatal blood cultures. The placental and neonatal isolates were both found to be serotype d by PCR, and were indistinguishable by PFGE. PMID:19926730

  14. Anti-inflammatory effect of Momordica charantia in sepsis mice.

    PubMed

    Chao, Che-Yi; Sung, Ping-Jyun; Wang, Wei-Hsien; Kuo, Yueh-Hsiung

    2014-01-01

    Wild bitter gourd (Momordica charantia L. var. abbreviate Seringe), a common vegetable in Asia, is used in traditional medicine to treat various diseases, including inflammation. Extant literature indicates that wild bitter gourds have components that activate PPARα and PPARγ. This research probed the influence of adding wild bitter gourd to diets on inflammation responses in mice with sepsis induced by intraperitoneal injection of LPS. Male BALB/c mice were divided normal, sepsis, positive control, and three experimental groups. The latter ate diets with low (1%), moderate (2%), and high (10%) ratios of wild bitter gourd lyophilized powder. Before mice were sacrificed, with the exception of the normal group, intraperitoneal injection of LPS induced sepsis in each group; positive control group was injected with LPS after PDTC. This experiment revealed starkly lower weights in groups with added wild bitter gourd than those of the remaining groups. Blood lipids (TG, cholesterol, and NEFA) were also lower in comparison to the sepsis group, and blood glucose concentrations recovered and approached normal levels. Blood biochemistry values related to inflammation reactions indicated GOT, GPT, C-RP, and NO concentrations of groups with added wild bitter gourd were all lower than those of the sepsis group. Secretion levels of the spleen pro-inflammatory cytokines IL-1, IL-6, and TNF-α tallied significantly lower in comparison to the sepsis group, whereas secretion levels of IL-10 anti-inflammatory cytokine increased. Expression level of proteins NF-κB, iNOS, and COX-2 were significantly inhibited. Results indicate wild bitter gourd in diets promoted lipid metabolism, reducing fat accumulation, and improving low blood glucose in sepsis. Addition of wild bitter gourd can reduce inflammation biochemical markers or indicators and pro-inflammatory cytokines in the body, hence improving the inflammation responses in mice with sepsis. PMID:25153878

  15. Heart Rate Variability in Porcine Progressive Peritonitis-Induced Sepsis

    PubMed Central

    Jarkovska, Dagmar; Valesova, Lenka; Chvojka, Jiri; Benes, Jan; Sviglerova, Jitka; Florova, Blanka; Nalos, Lukas; Matejovic, Martin; Stengl, Milan

    2016-01-01

    Accumulating evidence suggests that heart rate variability (HRV) alterations could serve as an indicator of sepsis progression and outcome, however, the relationships of HRV and major pathophysiological processes of sepsis remain unclear. Therefore, in this experimental study HRV was investigated in a clinically relevant long-term porcine model of severe sepsis/septic shock. HRV was analyzed by several methods and the parameters were correlated with pathophysiological processes of sepsis. In 16 anesthetized, mechanically ventilated, and instrumented domestic pigs of either gender, sepsis was induced by fecal peritonitis. Experimental subjects were screened up to the refractory shock development or death. ECG was continuously recorded throughout the experiment, afterwards RR intervals were detected and HRV parameters computed automatically using custom made measurement and analysis MATLAB routines. In all septic animals, progressive hyperdynamic septic shock developed. The statistical measures of HRV, geometrical measures of HRV and Poincaré plot analysis revealed a pronounced reduction of HRV that developed quickly upon the onset of sepsis and was maintained throughout the experiment. The frequency domain analysis demonstrated a decrease in the high frequency component and increase in the low frequency component together with an increase of the low/high frequency component ratio. The reduction of HRV parameters preceded sepsis-associated hemodynamic changes including heart rate increase or shock progression. In a clinically relevant porcine model of peritonitis-induced progressive septic shock, reduction of HRV parameters heralded sepsis development. HRV reduction was associated with a pronounced parasympathetic inhibition and a shift of sympathovagal balance. Early reduction of HRV may serve as a non-invasive and sensitive marker of systemic inflammatory syndrome, thereby widening the therapeutic window for early interventions. PMID:26779039

  16. A Review of GM-CSF Therapy in Sepsis.

    PubMed

    Mathias, Brittany; Szpila, Benjamin E; Moore, Frederick A; Efron, Philip A; Moldawer, Lyle L

    2015-12-01

    Determine what clinical role, if any, GM-CSF may have in the clinical treatment of sepsis in the adult patient. Advancements in the management of sepsis have led to significant decreases in early mortality; however, sepsis remains a significant source of long-term mortality and disability which places strain on healthcare resources with a substantial growing economic impact. Historically, early multiple organ failure (MOF) and death in patients with severe sepsis was thought to result from an exaggerated proinflammatory response called the systemic inflammatory response syndrome (SIRS). Numerous prospective randomized controlled trials (PRCTs) tested therapies aimed at decreasing the organ injury associated with an exaggerated inflammatory response. With few exceptions, the results from these PRCTs have been disappointing, and currently no specific therapeutic agent is approved to counteract the early SIRS response in patients with severe sepsis. It has long been recognized that there is a delayed immunosuppressive state that contributes to long-term morbidity. However, recent findings now support a concurrent proinflammatory and anti-inflammatory response present throughout sepsis. Multiple immunomodulating agents have been studied to combat the immunosuppressive phase of sepsis with the goal of decreasing secondary infection, reducing organ dysfunction, decreasing ICU stays, and improving survival. Granulocyte-macrophage colony stimulating factor (GM-CSF), a myelopoietic growth factor currently used in patients with neutropenia secondary to chemotherapy-induced myelosuppression, has been studied as a potential immune-activating agent. The applicability of GM-CSF as a standard therapy for generalized sepsis is still largely understudied; however, small-scale studies available have demonstrated some improved recovery from infection, decreased hospital length of stay, decreased days requiring mechanical ventilation, and decreased medical costs. PMID:26683913

  17. PREMIER's imaging IR limb sounder

    NASA Astrophysics Data System (ADS)

    Kraft, Stefan; Caron, Jerome; Bézy, Jean-Loup; Meynart, Roland; Langen, Jörg; Carnicero Dominguez, Bernardo; Bensi, Paolo; Silvestrin, Pierluigi

    2011-11-01

    The Imaging IR Limb Sounder (IRLS) is one of the two instruments planned on board of the candidate Earth Explorer Core Mission PREMIER. PREMIER stands for PRocess Exploration through Measurements of Infrared and Millimetrewave Emitted Radiation and is presently under feasibility study by ESA. Emerging from recent enhanced detector and processing technologies IRLS shall, next to a millimetre-wave limb sounder, explore the benefits of three-dimensional limb sounding with embedded cloud imaging capability. Such 3d imaging technology is expected to open a new era of limb sounding that will allow detailed studies of the link between atmospheric composition and climate, since it will map simultaneously fields of temperature and many trace gases in the mid/upper troposphere and stratosphere across a large vertical and horizontal field of view and with relatively high vertical and horizontal resolution. PREMIER shall fly in tandem formation looking backwards to METOP's swath and thereby explore the benefit of 3-dimensional information for meteorological/environmental analyses and climate forcing investigations. As currently planned and if implemented, IRLS will cover a total horizontal field of about 360 km and observe the limb at altitudes between 4 and 52 km. The vertical spatial sampling distance (SSD) will be well below 1 km. It will be run in two different exclusive modes to address scientific questions about atmospheric dynamics and chemistry at spectral samplings of ~1.2 cm-1 and ~0.2 cm-1, respectively. In such configuration IRLS will be composed of an imaging array with about 1800 macro pixels or sub-samples, thereby allowing cloud imaging and rejection at sufficient spatial resolution. We will present an overview of the instrument requirements as derived from the scientific requirements, the present status of the mission, and we will give an overview of the currently identified technology needs and instrument predevelopments.

  18. Betulin attenuates lung and liver injuries in sepsis.

    PubMed

    Zhao, Hongyu; Liu, Zhenning; Liu, Wei; Han, Xinfei; Zhao, Min

    2016-01-01

    Sepsis is a complex condition with unacceptable mortality. Betulin is a natural extract with multiple bioactivities. This study aims to evaluate the potential effects of betulin on lung and liver injury in sepsis. Cecal ligation and puncture was used to establish the rat model of sepsis. A single dose of 4mg/kg or 8mg/kg betulin was injected intraperitoneally immediately after the model establishment. The survival rate was recorded every 12h for 96h. The organ injury was examined using hematoxylin and eosin staining and serum biochemical test. The levels of proinflammatory cytokines and high mobility group box 1 in the serum were measured using ELISA. Western blotting was used to detect the expression of proteins in NF-κB and MAPK signaling pathways. Betulin treatment significantly improved the survival rate of septic rats, and attenuated lung and liver injury in sepsis, including the reduction of lung wet/dry weight ratio and activities of alanine aminotransferase and aspartate aminotransferase in the serum. In addition, levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and high mobility group box 1 in the serum were also lowered by betulin treatment. Moreover, sepsis-induced activation of the NF-κB and MAPK signaling pathway was inhibited by betulin as well. Our findings demonstrate the protective effect of betulin in lung and liver injury in sepsis. This protection may be mediated by its anti-inflammatory and NF-κB and MAPK inhibitory effects. PMID:26644168

  19. New Approaches to Sepsis: Molecular Diagnostics and Biomarkers

    PubMed Central

    Bauer, Michael; Riedemann, Niels C.; Hartog, Christiane S.

    2012-01-01

    Summary: Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies. PMID:23034322

  20. Circulating MicroRNAs as Biomarkers for Sepsis

    PubMed Central

    Benz, Fabian; Roy, Sanchari; Trautwein, Christian; Roderburg, Christoph; Luedde, Tom

    2016-01-01

    Sepsis represents a major cause of lethality during intensive care unit (ICU) treatment. Pharmacological treatment strategies for sepsis are still limited and mainly based on the early initiation of antibiotic and supportive treatment. In this context, numerous clinical and serum based markers have been evaluated for the diagnosis, the severity, and the etiology of sepsis. However until now, few of these factors could be translated into clinical use. MicroRNAs (miRNAs) do not encode for proteins but regulate gene expression by inhibiting the translation or transcription of their target mRNAs. Recently it was demonstrated that miRNAs are released into the circulation and that the spectrum of circulating miRNAs might be altered during various pathologic conditions, such as inflammation, infection, and sepsis. By using array- and single PCR-based methods, a variety of deregulated miRNAs, including miR-25, miR-133a, miR-146, miR-150, and miR-223, were described in the context of sepsis. Some of the miRNAs correlated with the disease stage, as well as patients’ short and long term prognosis. Here, we summarize the current findings on the role of circulating miRNAs in the diagnosis and staging of sepsis in critically ill patients. We compare data from patients with findings from animal models and, finally, highlight the challenges and drawbacks that currently prevent the use of circulating miRNAs as biomarkers in clinical routine. PMID:26761003

  1. Mechanisms of neutropenia involving myeloid maturation arrest in burn sepsis.

    PubMed Central

    Shoup, M; Weisenberger, J M; Wang, J L; Pyle, J M; Gamelli, R L; Shankar, R

    1998-01-01

    OBJECTIVE: To determine the mechanisms that lead to the decrease in bone marrow production of neutrophils during burn sepsis. SUMMARY BACKGROUND DATA: Impaired bone marrow granulopoiesis during burn sepsis often results in neutropenia despite elevated circulating levels of granulocyte colony-stimulating factor (G-CSF). To date, neither the specific stages of neutrophil maturation involved in the bone marrow suppression nor the mechanisms for the impairment have been determined. METHODS: Peripheral blood absolute neutrophil count and G-CSF levels were determined in mice 3 days after randomization to control, burn alone, or burn plus a topical inoculation of Pseudomonas aeruginosa (1000 colony-forming units). Bone marrow aspirates were analyzed for their neutrophil differentiation patterns by Gr-1 antigen expression and their G-CSF receptor status. Histologic analysis of liver, lung, spleen, and wound site was performed. RESULTS: In burn sepsis, absolute neutrophil count was reduced whereas plasma G-CSF levels were elevated, and myeloid differentiation was significantly shifted toward the immature mitotic myeloid cells. Bone marrow G-CSF receptor mRNA levels and G-CSF-stimulated proliferation were substantially decreased in burn sepsis. Histologic analysis revealed no significant neutrophil infiltration into the tissues. CONCLUSIONS: In thermal injury with superimposed sepsis, neutropenia and myeloid maturation arrest, despite the elevated levels of G-CSF, correlate with the reduction in bone marrow G-CSF receptor expression. These observations may provide a potential mechanism for neutropenia in sepsis. Images Figure 5. Figure 6. Figure 8. Figure 9. PMID:9671075

  2. HMGB1 Mediates Anemia of Inflammation in Murine Sepsis Survivors

    PubMed Central

    Valdés-Ferrer, Sergio I; Papoin, Julien; Dancho, Meghan E; Olofsson, Peder S; Li, Jianhua; Lipton, Jeffrey M; Avancena, Patricia; Yang, Huan; Zou, Yong-Rui; Chavan, Sangeeta S; Volpe, Bruce T; Gardenghi, Sara; Rivella, Stefano; Diamond, Betty; Andersson, Ulf; Steinberg, Bettie M; Blanc, Lionel; Tracey, Kevin J

    2015-01-01

    Patients surviving sepsis develop anemia, but the molecular mechanism is unknown. Here we observed that mice surviving polymicrobial gram-negative sepsis develop hypochromic, microcytic anemia with reticulocytosis. The bone marrow of sepsis survivors accumulates polychromatophilic and orthochromatic erythroblasts. Compensatory extramedullary erythropoiesis in the spleen is defective during terminal differentiation. Circulating tumor necrosis factor (TNF) and interleukin (IL)-6 are elevated for 5 d after the onset of sepsis, and serum high-mobility group box 1 (HMGB1) levels are increased from d 7 until at least d 28. Administration of recombinant HMGB1 to healthy mice mediates anemia with extramedullary erythropoiesis and significantly elevated reticulocyte counts. Moreover, administration of anti-HMGB1 monoclonal antibodies after sepsis significantly ameliorates the development of anemia (hematocrit 48.5 ± 9.0% versus 37.4 ± 6.1%, p < 0.01; hemoglobin 14.0 ± 1.7 versus 11.7 ± 1.2 g/dL, p < 0.01). Together, these results indicate that HMGB1 mediates anemia by interfering with erythropoiesis, suggesting a potential therapeutic strategy for anemia in sepsis. PMID:26736178

  3. Selecting patients with severe sepsis for drotrecogin alfa (activated) therapy.

    PubMed

    Sollet, Jean-Pierre; Garber, Gary E

    2002-12-01

    Selecting patients for drotrecogin alfa (activated) (Xigris; Eli Lilly and Company, Indianapolis, IN) therapy outside of a clinical trial setting requires knowledge of the rationale that led the Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) investigators to select the various entry criteria for the trial. Enrollment criteria for the study included a known or suspected infection, presence of at least 3 systemic inflammatory response syndrome (SIRS) criteria, and dysfunction of > or =1 organ or system. The infection criteria used in PROWESS were designed to be straightforward and were based on common clinical and radiological data. Although previous definitions of sepsis required only 2 SIRS criteria, the PROWESS trial investigators required the presence of > or =3 SIRS criteria to improve the sensitivity and specificity of these criteria for the diagnosis of sepsis. Acute organ dysfunction, the diagnostic criterion for severe sepsis, was used to define the study population because it identifies patients at significant risk of death. Characteristics of drotrecogin alfa (activated)-treated patients, including infection, modified SIRS criteria, and organ dysfunction, were similar to those of the placebo group and the general sepsis population. Proper clinical judgment and use of the these inclusion criteria as a guide will help clinicians select and treat sepsis patients with drotrecogin alfa (activated). PMID:12521613

  4. Role of Circulating Lymphocytes in Patients with Sepsis

    PubMed Central

    de Pablo, Raul; Monserrat, Jorge; Prieto, Alfredo; Alvarez-Mon, Melchor

    2014-01-01

    Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed. PMID:25302303

  5. Sepsis-induced elevation in plasma serotonin facilitates endothelial hyperpermeability

    PubMed Central

    Li, Yicong; Hadden, Coedy; Cooper, Anthonya; Ahmed, Asli; Wu, Hong; Lupashin, Vladimir V.; Mayeux, Philip R.; Kilic, Fusun

    2016-01-01

    Hyperpermeability of the endothelial barrier and resulting microvascular leakage are a hallmark of sepsis. Our studies describe the mechanism by which serotonin (5-HT) regulates the microvascular permeability during sepsis. The plasma 5-HT levels are significantly elevated in mice made septic by cecal ligation and puncture (CLP). 5-HT-induced permeability of endothelial cells was associated with the phosphorylation of p21 activating kinase (PAK1), PAK1-dependent phosphorylation of vimentin (P-vimentin) filaments, and a strong association between P-vimentin and ve-cadherin. These findings were in good agreement with the findings with the endothelial cells incubated in serum from CLP mice. In vivo, reducing the 5-HT uptake rates with the 5-HT transporter (SERT) inhibitor, paroxetine blocked renal microvascular leakage and the decline in microvascular perfusion. Importantly, mice that lack SERT showed significantly less microvascular dysfunction after CLP. Based on these data, we propose that the increased endothelial 5-HT uptake together with 5-HT signaling disrupts the endothelial barrier function in sepsis. Therefore, regulating intracellular 5-HT levels in endothelial cells represents a novel approach in improving sepsis-associated microvascular dysfunction and leakage. These new findings advance our understanding of the mechanisms underlying cellular responses to intracellular/extracellular 5-HT ratio in sepsis and refine current views of these signaling processes during sepsis. PMID:26956613

  6. New approaches to sepsis: molecular diagnostics and biomarkers.

    PubMed

    Reinhart, Konrad; Bauer, Michael; Riedemann, Niels C; Hartog, Christiane S

    2012-10-01

    Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies. PMID:23034322

  7. 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

  8. Managing residual limb hyperhidrosis in wounded warriors.

    PubMed

    Pace, Sarah; Kentosh, Joshua

    2016-06-01

    Residual limb dermatologic problems are a common concern among young active traumatic amputee patients who strive to maintain an active lifestyle. Hyperhidrosis of residual limbs is a recognized inciting factor that often contributes to residual limb dermatoses and is driven by the design of the prosthetic liner covering the residual limb. Treatment of hyperhidrosis in this population presents a unique challenge. Several accepted treatments of hyperhidrosis can offer some relief but have been limited by lack of results or side-effect profiles. Microwave thermal ablation has presented an enticing potential for residual limb hyperhidrosis. PMID:27416083

  9. 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

  10. Late-onset neonatal sepsis: recent developments

    PubMed Central

    Dong, Ying; Speer, Christian P

    2015-01-01

    The incidence of neonatal late-onset sepsis (LOS) is inversely related to the degree of maturity and varies geographically from 0.61% to 14.2% among hospitalised newborns. Epidemiological data on very low birth weight infants shows that the predominant pathogens of neonatal LOS are coagulase-negative staphylococci, followed by Gram-negative bacilli and fungi. Due to the difficulties in a prompt diagnosis of LOS and LOS-associated high risk of mortality and long-term neurodevelopmental sequelae, empirical antibiotic treatment is initiated on suspicion of LOS. However, empirical therapy is often inappropriately used with unnecessary broad-spectrum antibiotics and a prolonged duration of treatment. The increasing number of multidrug-resistant Gram-negative micro-organisms in neonatal intensive care units (NICU) worldwide is a serious concern, which requires thorough and efficient surveillance strategies and appropriate treatment regimens. Immunological strategies for preventing neonatal LOS are not supported by current evidence, and approaches, such as a strict hygiene protocol and the minimisation of invasive procedures in NICUs represent the cornerstone to reduce the burden of neonatal LOS. PMID:25425653

  11. Development and the evolvability of human limbs

    PubMed Central

    Young, Nathan M.; Wagner, Günter P.; Hallgrímsson, Benedikt

    2010-01-01

    The long legs and short arms of humans are distinctive for a primate, the result of selection acting in opposite directions on each limb at different points in our evolutionary history. This mosaic pattern challenges our understanding of the relationship of development and evolvability because limbs are serially homologous and genetic correlations should act as a significant constraint on their independent evolution. Here we test a developmental model of limb covariation in anthropoid primates and demonstrate that both humans and apes exhibit significantly reduced integration between limbs when compared to quadrupedal monkeys. This result indicates that fossil hominins likely escaped constraints on independent limb variation via reductions to genetic pleiotropy in an ape-like last common ancestor (LCA). This critical change in integration among hominoids, which is reflected in macroevolutionary differences in the disparity between limb lengths, facilitated selection for modern human limb proportions and demonstrates how development helps shape evolutionary change. PMID:20133636

  12. Impact of sepsis on CD4 T cell immunity

    PubMed Central

    Cabrera-Perez, Javier; Condotta, Stephanie A.; Badovinac, Vladimir P.; Griffith, Thomas S.

    2014-01-01

    Sepsis remains the primary cause of death from infection in hospital patients, despite improvements in antibiotics and intensive-care practices. Patients who survive severe sepsis can display suppressed immune function, often manifested as an increased susceptibility to (and mortality from) nosocomial infections. Not only is there a significant reduction in the number of various immune cell populations during sepsis, but there is also decreased function in the remaining lymphocytes. Within the immune system, CD4 T cells are important players in the proper development of numerous cellular and humoral immune responses. Despite sufficient clinical evidence of CD4 T cell loss in septic patients of all ages, the impact of sepsis on CD4 T cell responses is not well understood. Recent findings suggest that CD4 T cell impairment is a multipronged problem that results from initial sepsis-induced cell loss. However, the subsequent lymphopenia-induced numerical recovery of the CD4 T cell compartment leads to intrinsic alterations in phenotype and effector function, reduced repertoire diversity, changes in the composition of naive antigen-specific CD4 T cell pools, and changes in the representation of different CD4 T cell subpopulations (e.g., increases in Treg frequency). This review focuses on sepsis-induced alterations within the CD4 T cell compartment that influence the ability of the immune system to control secondary heterologous infections. The understanding of how sepsis affects CD4 T cells through their numerical loss and recovery, as well as function, is important in the development of future treatments designed to restore CD4 T cells to their presepsis state. PMID:24791959

  13. Evaluation of Vitamin C for Adjuvant Sepsis Therapy

    PubMed Central

    2013-01-01

    Abstract Significance: Evidence is emerging that parenteral administration of high-dose vitamin C may warrant development as an adjuvant therapy for patients with sepsis. Recent Advances: Sepsis increases risk of death and disability, but its treatment consists only of supportive therapies because no specific therapy is available. The characteristics of severe sepsis include ascorbate (reduced vitamin C) depletion, excessive protein nitration in microvascular endothelial cells, and microvascular dysfunction composed of refractive vasodilation, endothelial barrier dysfunction, and disseminated intravascular coagulation. Parenteral administration of ascorbate prevents or even reverses these pathological changes and thereby decreases hypotension, edema, multiorgan failure, and death in animal models of sepsis. Critical Issues: Dehydroascorbic acid appears to be as effective as ascorbate for protection against microvascular dysfunction, organ failure, and death when injected in sepsis models, but information about pharmacodynamics and safety in human subjects is only available for ascorbate. Although the plasma ascorbate concentration in critically ill and septic patients is normalized by repletion protocols that use high doses of parenteral ascorbate, and such doses are tolerated well by most healthy subjects, whether such large amounts of the vitamin trigger adverse effects in patients is uncertain. Future Directions: Further study of sepsis models may determine if high concentrations of ascorbate in interstitial fluid have pro-oxidant and bacteriostatic actions that also modify disease progression. However, the ascorbate depletion observed in septic patients receiving standard care and the therapeutic mechanisms established in models are sufficient evidence to support clinical trials of parenteral ascorbate as an adjuvant therapy for sepsis. Antioxid. Redox Signal. 19, 2129–2140. PMID:23682970

  14. Early and Late Onset Sepsis in Late Preterm Infants

    PubMed Central

    Cohen-Wolkowiez, Michael; Moran, Cassandra; Benjamin, Daniel K.; Cotten, C. Michael; Clark, Reese H.; Benjamin, Daniel K.; Smith, P. Brian

    2009-01-01

    Background Preterm birth is increasing worldwide, and late preterm births, which comprise more than 70% of all preterm births, account for much of the increase. Early and late onset sepsis results in significant mortality in extremely preterm infants, but little is known about sepsis outcomes in late preterm infants. Methods This is an observational cohort study of infants < 121 days of age (119,130 infants less than or equal to 3 days of life and 106,142 infants between 4 and 120 days of life) with estimated gestational age at birth between 34 and 36 weeks, admitted to 248 neonatal intensive care units in the United States between 1996 and 2007. Results During the study period, the cumulative incidence of early and late onset sepsis was 4.42 and 6.30 episodes per 1000 admissions, respectively. Gram-positive organisms caused the majority of early and late onset sepsis episodes. Infants with early onset sepsis caused by Gram-negative rods and infants with late onset sepsis were more likely to die than their peers with sterile blood cultures (OR 4.39, 95% CI 1.71–11.23, P=0.002; and OR 3.37, 95% CI 2.35–4.84, P<0.001, respectively). Conclusion Late preterm infants demonstrate specific infection rates, pathogen distribution, and mortality associated with early and late onset sepsis. The results of this study are generalizable to late preterm infants admitted to the special care nursery or neonatal intensive care unit. PMID:19953725

  15. HLA-DR expression, cytokines and bioactive lipids in sepsis

    PubMed Central

    2014-01-01

    Sepsis accounts for more than 200,000 deaths annually in the USA alone. Both inflammatory and anti-inflammatory responses occur simultaneously in sepsis, the early phase dominated by the hyperinflammatory response and the late phase by immunosuppression. This late immunosuppression phase leads to loss of the delayed type hypersensitivity response, failure to clear the primary infection and development of secondary infections. Based on the available data, I hypothesize that failure to produce adequate amounts of inflammation resolving lipid mediators may be at the centre of both the hyperinflammatory response and late immunosuppression seen in sepsis. These proresolving lipids – lipoxins, resolvins and protectins – suppress exacerbated activation of leukocytes and macrophages, inhibit excess production of pro-inflammatory cytokines, initiate resolution of inappropriate inflammation, augment clearance of bacteria and other pathogens, and restore homeostasis. If true, this implies that administration of naturally occurring lipoxins, resolvins, protectins, maresins and nitrolipids by themselves or their more stable synthetic analogues such as 15-epi-16-(para-fluorophenoxy)-lipoxin A4-methyl ester, a synthetic analogue of 15-epi-lipoxin A4, and 15(R/S)-methyl-LXA4 may form a new approach in the prevention (in the high-risk subjects), management of sepsis and in resolving the imbalanced inflammatory process such that sepsis is ameliorated early. In addition, recent studies have suggested that nociceptin and cold inducible RNA binding protein (CIRBP) also have a role in the pathobiology of sepsis. It is suggested that both nociceptin and CIRBP inhibit the production of lipoxins, resolvins, protectins, maresins, and nitrolipids and thus play a role in sepsis and septic shock. PMID:24904669

  16. Serum Procalcitonine Levels as an Early Diagnostic Indicator of Sepsis

    PubMed Central

    Beqja-Lika, Anila; Bulo-Kasneci, Anyla; Refatllari, Etleva; Heta-Alliu, Nevila; Rucaj-Barbullushi, Alma; Mone, Iris; Mitre, Anila

    2013-01-01

    Introduction: Prompt and accurate diagnosis of sepsis is of high importance for clinicians. Procalcitonine (PCT) and C-reactive protein (CRP) have been proposed as markers for this purpose. Our aim was to evaluate the levels of PCT and CRP in early sepsis and its correlation with severity of sepsis. Methods: Levels of PCT and CRP were taken from 60 patients with sepsis criteria and 39 patients with SIRS symptoms from the University Hospital Center “Mother Teresa” in Tirana, Albania during 2010-2012. Sensitivity, specificity and predictive values for PCT and CRP were calculated. Results: PCT and CRP levels increased in parallel with the severity of the clinical conditions of the patients. The mean PCT level in patients with sepsis was 11.28 ng/ml versus 0.272 ng/ml in patients with SIRS symptoms, with a sensitivity of 97.4% and a specificity of 96.6% for PCT >0.5ng/ml. The mean CRP level in septic patients was 146.58 mg/l vs. 34.4 mg/l in patients with SIRS, with a sensitivity of 98.6% for sepsis and a specificity of 75 % for CRP >11mg/l. Conclusion: PCT and CRP values are useful markers to determine early diagnosis and severity of an infection. In the present study, PCT was found to be a more accurate diagnostic parameter for differentiating SIRS from sepsis and may be helpful in the follow-up of critically ill patients. PMID:23687457

  17. Systematic review of use of β-blockers in sepsis

    PubMed Central

    Chacko, Cyril Jacob; Gopal, Shameer

    2015-01-01

    Background and Aims: We proposed a review of present literature and systematic analysis of present literature to summarize the evidence on the use of β-blockers on the outcome of a patient with severe sepsis and septic shock. Material and Methods: Medline, EMBASE, Cochrane Library were searched from 1946 to December 2013. The bibliography of all relevant articles was hand searched. Full-text search of the grey literature was done through the medical institution database. The database search identified a total of 1241 possible studies. The citation list was hand searched by both the authors. A total of 9 studies were identified. Results: Most studies found a benefit from β-blocker administration in sepsis. This included improved heart rate (HR) control, decreased mortality and improvement in acid-base parameters. Chronic β-blocker usage in sepsis was also associated with improved mortality. The administration of β-blockers during sepsis was associated with better control of HR. The methodological quality of all the included studies, however, was poor. Conclusion: There is insufficient evidence to justify the routine use of β-blockers in sepsis. A large adequately powered multi-centered randomized controlled clinical trial is required to address the question on the efficacy of β-blocker usage in sepsis. This trial should also consider a number of important questions including the choice of β-blocker used, optimal dosing, timing of intervention, duration of intervention and discontinuation of the drug. Until such time based on the available evidence, there is no place for the use of β-blockers in sepsis in current clinical practice. PMID:26702201

  18. A Rare Case of Fatal Endocarditis and Sepsis Caused by Pseudomonas aeruginosa in a Patient with Chronic Renal Failure

    PubMed Central

    Vijan, Vikrant; Vupputuri, Anjith; Nandakumar, Sandya; Mathew, Navin

    2016-01-01

    Nosocomial catheter-related and Arteriovenous fistula (AV)-related infections are significant concern in patients undergoing haemodialysis. These infections are associated with multiple complications as well as mortality and demands immediate and appropriate management. While coagulase-negative staphylococci, S.aureus, and Escherichia coli are the most common causes of catheter-related infections in haemodialysis patients, such infections caused by Pseudomonas aeruginosa are relatively rare. Here, we present an unusual case of 36-year-old male patient with chronic renal failure, who developed endocarditis and sepsis from Pseudomonas aeruginosa infection of the left hand arteriovenous fistula. The bacteraemia in the present case caused multiple complications including dry gangrene of bilateral lower limbs, stroke, endophthalmitis, left brachial artery thrombosis and vegetations on the interventricular septum and aortic wall. Despite antibiotic treatment, the patient suffered a cardiac arrest and could not be revived.

  19. The OMPS Limb Profiler instrument

    NASA Astrophysics Data System (ADS)

    Rault, D. F.; Xu, P.

    2011-12-01

    The Ozone Mapping and Profiler Suite (OMPS) will continue the monitoring of the global distribution of the Earth's middle atmosphere ozone and aerosol. OMPS is composed of three instruments, namely the Total Column Mapper (heritage: TOMS, OMI), the Nadir Profiler (heritage: SBUV) and the Limb Profiler (heritage: SOLSE/LORE, OSIRIS, SCIAMACHY, SAGE III). The ultimate goal of the mission is to better understand and quantify the rate of stratospheric ozone recovery. OMPS is scheduled to be launched on the NPOESS Preparatory Project (NPP) platform in October 2011. The focus of the paper will be on the Limb Profiler (LP) instrument. The LP instrument will measure the Earth's limb radiance, from which ozone profile will be retrieved from the upper tropopause uo to 60km. End-to-end studies of the sensor and retrieval algorithm indicate the following expected performance for ozone: accuracy of 5% or better from the tropopause up to 50 km, precision of about 3-5% from 18 to 50 km, and vertical resolution of 1.5-2 km with vertical sampling of 1 km and along-track horizontal sampling of 1 deg latitude. The paper will describe the mission, discuss the retrieval algorithm, and summarize the expected performance. If available, the paper will also present early on-orbit data.

  20. Synaesthesia in the normal limb.

    PubMed Central

    Mon-Williams, M; Wann, J P; Jenkinson, M; Rushton, K

    1997-01-01

    We explored the degree to which vision may alter kinaesthetic perception by asking participants to view their hand through a prism, introducing different horizontal deviations, while trying to align their fingers above and below a thin table. When the visual image of one hand was displaced this overwhelmed kinaesthetic judgements and participants reliably reported that they felt their limbs were aligned, even when they were laterally mis-aligned by as much as 10 cm. This effect, however, was mediated by 'visual capture' and when the task was attempted in a darkened room with limb position indicated by an LED taped to the finger, kinaesthesis dominated and participants reported that the LED seemed to become detached from their finger tip. In both light and dark conditions the finger was clearly visible and only the background detail was extinguished. Hence, in perceiving limb position, it appears that we believe in what we see, rather than in what we feel, when the visual background is rich, and in what we feel when the visual background is sparse. PMID:9263468

  1. Gremlin1 induces anterior-posterior limb bifurcations in developing Xenopus limbs but does not enhance limb regeneration.

    PubMed

    Wang, Yi-Hsuan; Keenan, Samuel R; Lynn, Jeremy; McEwan, James C; Beck, Caroline W

    2015-11-01

    Gremlin1 (grem1) has been previously identified as being significantly up-regulated during regeneration of Xenopus laevis limbs. Grem1 is an antagonist of bone morphogenetic proteins (BMPs) with a known role in limb development in amniotes. It forms part of a self-regulating feedback loop linking epithelial (FGF) and mesenchymal (shh) signalling centres, thereby controlling outgrowth, anterior posterior and proximal distal patterning. Spatiotemporal regulation of the same genes in developing and regenerating Xenopus limb buds supports conservation of this mechanism. Using a heat shock inducible grem1 (G) transgene to created temperature regulated stable lines, we have shown that despite being upregulated in regeneration, grem1 overexpression does not enhance regeneration of tadpole hindlimbs. However, both the regenerating and contralateral, developing limb of G transgenics developed skeletal defects, suggesting that overexpressing grem1 negatively affects limb patterning. When grem1 expression was targeted earlier in limb bud development, we saw dramatic bifurcations of the limbs resulting in duplication of anterior posterior (AP) pattern, forming a phenotypic continuum ranging from duplications arising at the level of the femoral head to digit bifurcations, but never involving the pelvis. Intriguingly, the original limbs have AP pattern inversion due to de-restricted Shh signalling. We discuss a possible role for Grem1 regulation of limb BMPs in regulation of branching pattern in the limbs. PMID:26527308

  2. Use of a virtual integrated environment in prosthetic limb development and phantom limb pain.

    PubMed

    Alphonso, Aimee L; Monson, Brett T; Zeher, Michael J; Armiger, Robert S; Weeks, Sharon R; Burck, J M; Moran, C; Davoodie, R; Loeb, G; Pasquina, Paul F; Tsao, Jack W

    2012-01-01

    Patients face two major difficulties following limb loss: phantom limb pain (PLP) in the residual limb and limited functionality in the prosthetic limb. Many studies have focused on decreasing PLP with mirror therapy, yet few have examined the same visual ameliorating effect with a virtual or prosthetic limb. Our study addresses the following key questions: (1) does PLP decrease through observation of a 3D limb in a virtual integration environment (VIE) and (2) can consistent surface electromyography (sEMG) signals from the VIE drive an advanced modular prosthetic limb (MPL)? Recorded signals from the residual limb were correlated to the desired motion of the phantom limb, and changes in PLP were scored during each VIE session. Preliminary results show an overall reduction in PLP and a trend toward improvement in signal-to-motion accuracy over time. These signals allowed MPL users to perform a wide range of hand motions. PMID:22954877

  3. Antithrombotic agents in the treatment of severe sepsis.

    PubMed

    Iqbal, Omer; Messmore, Harry; Fareed, Jawed; Ahmad, Sarfraz; Hoppensteadt, Debra; Hazar, Shadid; Tobu, Mahmut; Aziz, Salim; Wehrmacher, William

    2002-05-01

    Sepsis, a systemic inflammatory syndrome, is a response to infection and when associated with multiple organ dysfunction is termed severe sepsis. It remains a leading cause of mortality in the critically ill. The response to the invading microorganisms may be considered as a balance between a pro-inflammatory and an anti-inflammatory reaction. While an inadequate pro-inflammatory reaction and a strong anti-inflammatory response could lead to overwhelming infection and the death of the patient, a strong and uncontrolled pro-inflammatory response, manifested by the release of pro-inflammatory mediators may lead to microvascular thrombosis and multiple organ failure. Endotoxin triggers sepsis via the release of various mediators such as tumour necrosis factor-alpha and interleukin-1 (IL-1). These cytokines activate the complement and coagulation systems, release adhesion molecules, prostaglandins, leukotrienes, reactive oxygen species and nitric oxide. Other mediators involved in the sepsis syndrome include IL-1, -6 and -8; arachidonic acid metabolites; platelet activating factor; histamine; bradykinin; angiotensin; complement components and vasoactive intestinal peptide. These pro-inflammatory responses are counteracted by IL-10. Most of the trials targeting the different mediators of the pro-inflammatory response have failed due to a lack of correct definition of sepsis. Understanding the exact pathophysiology of the disease will enable more advanced treatment options. Targeting the coagulation system with various anticoagulant agents including, activated protein C, and tissue factor pathway inhibitor (TFPI) is a rational approach. Many clinical trials have been conducted to evaluate these agents in severe sepsis. While trials on antithrombin and TFPI were not so successful, the double-blind, placebo-controlled, Phase III trial of recombinant human activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) was successful, creating a significant decrease in

  4. 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

  5. Blood Culture Proven Early Onset Sepsis and Late Onset Sepsis in Very-Low-Birth-Weight Infants in Korea

    PubMed Central

    Lee, Soon Min; Chang, Meayoung

    2015-01-01

    Neonatal sepsis remains one of the most important causes of death and co-morbidity in very-low-birth-weight (VLBW) infants. The aim of this study was to determine the current incidences of early-onset sepsis (EOS) and late-onset sepsis (LOS), the distribution of pathogens, and the impact of infection on co-morbidities in VLBW infants. We analyzed the data including sepsis episode from 2,386 VLBW infants enrolled in Korean Neonatal Network from January 2013 to June 2014. We defined EOS as a positive blood culture occurring between birth and 7 days of life and LOS after 7 days of life. Sepsis was found in 21.1% of VLBW infants. The risk of sepsis was inversely related to birth weight and gestational age. EOS was found in only 3.6% of VLBW infants, however the mortality rate was as high as 34.1%. EOS was associated with the increased odds for bronchopulmonary dysplasia and intraventricular hemorrhage. The vast majority of EOS was caused by Gram-positive organisms, particularly coagulase-negative staphylococci (30.6%). LOS developed in 19.4% of VLBW infants with a 16.1% mortality rate. Pathogens in LOS were dominated by coagulase-negative staphylococci (38.3%). Twenty-five percent and fifty percent of first LOS episode occurred after 12 days and 20 days from birth, respectively. Younger and smaller VLBW infants showed the earlier occurrence day for the 25% of first LOS episode. This study provides a recent nationwide epidemiology of sepsis in VLBW infants in Korea. Based on this study, successful strategies to reduce infections would improve survival and reduce morbidity. PMID:26566360

  6. Improving the management of sepsis in a district general hospital by implementing the ‘Sepsis Six’ recommendations

    PubMed Central

    Kumar, Prashant; Jordan, Mark; Caesar, Jenny; Miller, Sarah

    2015-01-01

    Sepsis is a common condition with a major global impact on healthcare resources and expenditure. The Surviving Sepsis Campaign has been vigorous in promoting internationally recognised pathways to improve the management of septic patients and decrease mortality. However, translating recommendations into practice is a challenging and complex task that requires a multi-faceted approach with sustained engagement from local stakeholders. Whilst working at a district general hospital in New Zealand, we were concerned by the seemingly inconsistent management of septic patients, often leading to long delays in the initiation of life-saving measures such as antibiotic, fluid, and oxygen administration. In our hospital there were no clear systems, protocols or guidelines in place for identifying and managing septic patients. We therefore launched the Sepsis Six resuscitation bundle of care in our hospital in an attempt to raise awareness amongst staff and improve the management of septic patients. We introduced a number of simple low-cost interventions that included educational sessions for junior doctors and nursing staff, as well as posters and modifications to phlebotomy trolleys that acted as visual reminders to implement the Sepsis Six bundle. Overall, we found there to a be a steady improvement in the delivery of the Sepsis Six bundle in septic patients with 63% of patients receiving appropriate care within one hour, compared to 29% prior to our interventions. However this did not translate to an improvement in patient mortality. This project forms part of an on going process to instigate a fundamental culture change among local healthcare professionals regarding the management of sepsis. Whilst we have demonstrated improved implementation of the Sepsis Six bundle, the key challenge remains to ensure that momentum of this project continues and forms a platform for sustainable clinical improvement in the long term. PMID:26734403

  7. Phenotypic clusters within sepsis-associated multiple organ dysfunction syndrome

    PubMed Central

    Knox, Daniel B.; Lanspa, Michael J.; Kuttler, Kathryn G.; Brewer, Simon C.

    2015-01-01

    Introduction Sepsis is a devastating condition that is generally treated as a single disease. Identification of meaningfully distinct clusters may improve research, treatment and prognostication among septic patients. We therefore sought to identify clusters among patients with severe sepsis or septic shock. Methods We retrospectively studied all patients with severe sepsis or septic shock admitted directly from the emergency department to the intensive care units (ICUs) of three hospitals, 2006–2013. Using age and Sequential Organ Failure Assessment (SOFA) subscores, we defined clusters utilizing self-organizing maps, a method for representing multidimensional data in intuitive two-dimensional grids to facilitate cluster identification. Results We identified 2533 patients with severe sepsis or septic shock. Overall mortality was 17 %, with a mean APACHE II score of 24, mean SOFA score of 8 and a mean ICU stay of 5.4 days. Four distinct clusters were identified; (1) shock with elevated creatinine, (2) minimal multi-organ dysfunction syndrome (MODS), (3) shock with hypoxemia and altered mental status, and (4) hepatic disease. Mortality (95 % confidence intervals) for these clusters was 11 (8–14), 12 (11–14), 28 (25–32), and 21 (16–26) %, respectively (p < 0.0001). Regression modeling demonstrated that the clusters differed in the association between clinical outcomes and predictors, including APACHE II score. Conclusions We identified four distinct clusters of MODS among patients with severe sepsis or septic shock. These clusters may reflect underlying pathophysiological differences and could potentially facilitate tailored treatments or directed research. PMID:25851384

  8. Proteome changes in mesenteric lymph induced by sepsis

    PubMed Central

    ZHANG, PING; LI, YAN; ZHANG, LIAN-DONG; WANG, LIANG-HUA; WANG, XI; HE, CHAO; LIN, ZHAO-FEN

    2014-01-01

    The present study aimed to examine the changes in mesenteric lymph during the development of sepsis and to identify the distinct proteins involved, as targets for further study. The sepsis animal model was constructed by cecal ligation and puncture (CLP). The mesenteric lymph was collected from 28 adult male Sprague-Dawley rats, which were randomly divided into the following four groups (n=7 per group): CLP-6 h, CLP-24 h, sham-6 h and sham-24 h groups. Capillary high performance liquid chromatography-tandem mass spectrometry was performed to analyze the proteome in mesenteric lymph. A comprehensive bioinformatic analysis was then conducted to investigate the distinct proteins. Compared with the sham group, 158 distinct proteins were identified in the lymph samples from the CLP group. Five of these proteins associated with the same lipid metabolism pathway were selected, apolipoprotein E (ApoE), annexin A1 (Anxa1), neutrophil gelatinase-associated lipocalin (NGAL), S100a8 and S100a9. The expression of ApoE, Anxa1, NGAL, S100a8 and S100a9 were all elevated in the progression of sepsis. The five proteins were reported to be closely associated with disease development and may be a potential target for the diagnosis and treatment of sepsis. In conclusion, identifying proteome changes in mesenteric lymph provides a novel perspective to understand the pathological mechanisms underlying sepsis. PMID:25242054

  9. Multi-analytical Approaches Informing the Risk of Sepsis

    NASA Astrophysics Data System (ADS)

    Gwadry-Sridhar, Femida; Lewden, Benoit; Mequanint, Selam; Bauer, Michael

    Sepsis is a significant cause of mortality and morbidity and is often associated with increased hospital resource utilization, prolonged intensive care unit (ICU) and hospital stay. The economic burden associated with sepsis is huge. With advances in medicine, there are now aggressive goal oriented treatments that can be used to help these patients. If we were able to predict which patients may be at risk for sepsis we could start treatment early and potentially reduce the risk of mortality and morbidity. Analytic methods currently used in clinical research to determine the risk of a patient developing sepsis may be further enhanced by using multi-modal analytic methods that together could be used to provide greater precision. Researchers commonly use univariate and multivariate regressions to develop predictive models. We hypothesized that such models could be enhanced by using multiple analytic methods that together could be used to provide greater insight. In this paper, we analyze data about patients with and without sepsis using a decision tree approach and a cluster analysis approach. A comparison with a regression approach shows strong similarity among variables identified, though not an exact match. We compare the variables identified by the different approaches and draw conclusions about the respective predictive capabilities,while considering their clinical significance.

  10. The role of MBL2 gene polymorphism in sepsis incidence

    PubMed Central

    Liu, Lei; Ning, Bo

    2015-01-01

    Aim: This case-control study was aimed to explore the role of mannose-binding lectin 2 (MBL2) gene rs1800450 polymorphism (codon 54 A/B, G230A) in the development of sepsis in Han Chinese. Methods: MBL2 rs1800450 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). MBL serum level was detected by enzyme-linked immunosorbent assay (ELISA). Associations between rs1800450 and sepsis susceptibility was detected by Chi-square test and represented by odds ratios (ORs) and 95% confidence intervals (CIs). Correlation of rs1800450 genotypes and MBL serum level was assessed using t test. Result: Variant A allele frequency was significantly observed in cases than that in controls, indicating a significant association with the susceptibility of sepsis (OR = 1.979, 95% CI = 1.200-3.262). GA genotype also relate to the onset of sepsis (OR = 2.090, 95% CI = 1.163-3.753). MBL serum concentrations were significantly different between case and control groups (P<0.001). Meanwhile, variant allele carriers had lower serum level compared with wild homozygous (P<0.001). Conclusion: Variant A allele in MBL2 gene rs1800450 polymorphism might increase the risk of sepsis via decrease the MBL serum level. PMID:26823854