Science.gov

Sample records for limb intracompartmental sepsis

  1. Sepsis

    MedlinePlus

    ... multiple organ systems, causing them to fail. If sepsis progresses to septic shock, blood pressure drops dramatically, which may lead to death. Anyone can develop sepsis, but it's most common and most dangerous in ...

  2. Sepsis

    PubMed Central

    Karnatovskaia, Lioudmila V.; Festic, Emir

    2012-01-01

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

  3. Influence of mechanical ventilation and sepsis on redox balance in diaphragm, myocardium, limb muscles, and lungs.

    PubMed

    Chacon-Cabrera, Alba; Rojas, Yeny; Martínez-Caro, Leticia; Vila-Ubach, Monica; Nin, Nicolas; Ferruelo, Antonio; Esteban, Andrés; Lorente, José A; Barreiro, Esther

    2014-12-01

    Mechanical ventilation (MV), using high tidal volumes (V(T)), causes lung (ventilator-induced lung injury [VILI]) and distant organ injury. Additionally, sepsis is characterized by increased oxidative stress. We tested whether MV is associated with enhanced oxidative stress in sepsis, the commonest underlying condition in clinical acute lung injury. Protein carbonylation and nitration, antioxidants, and inflammation (immunoblotting) were evaluated in diaphragm, gastrocnemius, soleus, myocardium, and lungs of nonseptic and septic (cecal ligation and puncture 24 hours before MV) rats undergoing MV (n = 7 per group) for 150 minutes using 3 different strategies (low V(T) [V(T) = 9 mL/kg], moderate V(T) [V(T) = 15 mL/kg], and high V(T) [V(T) = 25 mL/kg]) and in nonventilated control animals. Compared with nonventilated control animals, in septic and nonseptic rodents (1) diaphragms, limb muscles, and myocardium of high-V(T) rats exhibited a decrease in protein oxidation and nitration levels, (2) antioxidant levels followed a specific fiber-type distribution in slow- and fast-twitch muscles, (3) tumor necrosis factor α (TNF-α) levels were higher in respiratory and limb muscles, whereas no differences were observed in myocardium, and (4) in lungs, protein oxidation was increased, antioxidants were rather decreased, and TNF-α remained unmodified. In this model of VILI, oxidative stress does not occur in distant organs or skeletal muscles of rodents after several hours of MV with moderate-to-high V(T), whereas protein oxidation levels were increased in the lungs of the animals. Inflammatory events were moderately expressed in skeletal muscles and lungs of the MV rats. Concomitant sepsis did not strongly affect the MV-induced effects on muscles, myocardium, or lungs in the rodents.

  4. Quantitative measurement of intra-compartmental pressure of the leg in acute traumatic injury: As a routine trend

    PubMed Central

    Yadav, Anurag; Sikdar, Jyotirmay; Anand, Vikas; Singh, Ravinder; Sidhu, Vishal

    2015-01-01

    Background Experience and literature regarding complications of lower extremity compartment syndrome led us to hypothesize that delayed diagnosis and limb loss are potentially preventable events. Clinical examination does play a role, but quantification of compartment pressure reading serves as confirmation and determines the need for surgical intervention and provides the only objective data in case of conflict. Methods We performed a prospective study of all cases of closed tibial fractures presenting to our trauma centre over a 3-year period (January 2009–June 2012). Variables reviewed included intra-compartmental pressure readings, location of the fracture and development of subsequent compartment syndrome requiring fasciotomy. Patients were divided into (1) Group A – proximal tibial fracture, (2) Group B – diaphyseal fracture and (3) Group C – Pilon fracture. Values of the injured and uninjured leg were taken and the data analyzed using SPSS version 22. Results 168 (41 females and 127 males) cases were analyzed. Mean pressure readings of the fractured limb were higher in Group A compared to the other groups. The mean difference in pressure values between the injured and uninjured limb recorded were of 15.1 mm Hg (Group A), 13.8 mm Hg (Group B) and 13.3 mm Hg (Group C). Patients who eventually underwent fasciotomy were 5 (10.8%) in Group A, 8 (10.3%) in Group B and 3 (6.8%) in Group C, and had initial baseline pressure difference of >18.5 mm Hg. Conclusion These data underscore the importance of routine recording of initial intra-compartmental pressure and relation of difference in compartmental pressure between injured and uninjured limb to eventual development of compartment syndrome requiring fasciotomy. PMID:26566335

  5. Ultrasonographic Evaluation of the Prevalence of an Intracompartmental Septum in Patients With de Quervain's Disease.

    PubMed

    Sato, Junko; Ishii, Yoshinori; Noguchi, Hideo

    2016-01-01

    It has been reported that more patients with de Quervain's disease who had undergone surgical treatment had a septated dorsal compartment than did normal cadavers. The purpose of this study was to sonographically evaluate the prevalence of an intracompartmental septum in patients with de Quervain's disease and to compare the prevalence between groups categorized by sex, age, and peripartum status. The authors performed an ultrasonographic examination of 112 wrists from 103 patients with de Quervain's disease. The prevalence of a septum-like structure in the first compartment was compared between men and women, between older (≥40 years) and younger (≤39 years) patients, and between pregnant or lactating women and other patients. The prevalence of intracompartmental septum in patients with de Quervain's disease was 61.6% (69 of 112). Of the 69 wrists with an intracompartmental septum-like structure, 53 showed this structure completely through the level of the radial styloid, and 16 showed it partially on the level of the distal radial styloid. There was no significant difference between any 2 groups categorized by the patients' demographics. The prevalence of intracompartmental septation in the patients with de Quervain's disease was higher than the previously reported prevalence in cadavers and lower than that of patients who underwent surgery. This result was consistent with a previous report that patients with a septated dorsal compartment may be more at risk of contracting de Quervain's disease and more prone to failure of nonoperative treatment.

  6. Intracompartmental and intercompartmental transcriptional networks coordinate the expression of genes for organellar functions.

    PubMed

    Leister, Dario; Wang, Xi; Haberer, Georg; Mayer, Klaus F X; Kleine, Tatjana

    2011-09-01

    Genes for mitochondrial and chloroplast proteins are distributed between the nuclear and organellar genomes. Organelle biogenesis and metabolism, therefore, require appropriate coordination of gene expression in the different compartments to ensure efficient synthesis of essential multiprotein complexes of mixed genetic origin. Whereas organelle-to-nucleus signaling influences nuclear gene expression at the transcriptional level, organellar gene expression (OGE) is thought to be primarily regulated posttranscriptionally. Here, we show that intracompartmental and intercompartmental transcriptional networks coordinate the expression of genes for organellar functions. Nearly 1,300 ATH1 microarray-based transcriptional profiles of nuclear and organellar genes for mitochondrial and chloroplast proteins in the model plant Arabidopsis (Arabidopsis thaliana) were analyzed. The activity of genes involved in organellar energy production (OEP) or OGE in each of the organelles and in the nucleus is highly coordinated. Intracompartmental networks that link the OEP and OGE gene sets serve to synchronize the expression of nucleus- and organelle-encoded proteins. At a higher regulatory level, coexpression of organellar and nuclear OEP/OGE genes typically modulates chloroplast functions but affects mitochondria only when chloroplast functions are perturbed. Under conditions that induce energy shortage, the intercompartmental coregulation of photosynthesis genes can even override intracompartmental networks. We conclude that dynamic intracompartmental and intercompartmental transcriptional networks for OEP and OGE genes adjust the activity of organelles in response to the cellular energy state and environmental stresses, and we identify candidate cis-elements involved in the transcriptional coregulation of nuclear genes. Regarding the transcriptional regulation of chloroplast genes, novel tentative target genes of σ factors are identified.

  7. Pediatric Sepsis.

    PubMed

    Prusakowski, Melanie K; Chen, Audrey P

    2017-02-01

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

  8. Neonatal sepsis.

    PubMed

    Stefanovic, Iva Mihatov

    2011-01-01

    Neonatal sepsis is the most common cause of neonatal deaths with high mortality despite treatment. Neonatal sepsis can be classified into two subtypes depending upon onset of symptoms. There are many factors that make neonates more susceptable to infection. Signs of sepsis in neonates are often non-specific and high degree of suspicion is needed for early diagnosis. Some laboratory parameters can be helpful for screening of neonates with neonatal sepsis, but none of it is specific and sensitive enough to be used singly. Diagnostic approach mostly focuses on history and review of non specific signs and symptoms. Antibiotic treatment is the mainstay of treatment and supportive care is equally important. The aim of this review is to give an overview of neonatal sepsis, including incidence, etiology, clinical picture, diagnostics and therapy.

  9. Neonatal sepsis

    PubMed Central

    Shah, Birju A; Padbury, James F

    2014-01-01

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

  10. Dental sepsis.

    PubMed

    Mueller, P O; Lowder, M Q

    1998-08-01

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

  11. Evaluation of stress-related anterior lower leg pain with magnetic resonance imaging and intracompartmental pressure measurement.

    PubMed

    Kiuru, Martti J; Mantysaari, Matti J; Pihlajamaki, Harri K; Ahovuo, Juhani A

    2003-01-01

    The purpose of this work was to evaluate stress-related anterior lower leg pain with clinical examination, magnetic resonance imaging, and measurement of anterior tibial compartment pressure findings. All medical data were gathered from 24 conscripts with stress-related anterior lower leg pain. Twenty exhibited bilateral symptoms. In 22 of the 44 cases, the intracompartmental pressure was pathological. Symptoms were exhibited for longer periods by patients with chronic exertional compartment syndrome (CECS) than by other patients (p < 0.01). At rest, magnetic resonance imaging revealed no abnormal findings in the soft tissues of the legs but showed bone abnormalities in 35 symptomatic legs. Thirty-three exhibited bone stress injuries, and two exhibited leg traction periostitis. On magnetic resonance imaging, there was no difference in bone findings between patients with and without CECS (p > 0.05). Stress-related anterior lower leg pain can be related to CECS, bone stress injury, and traction periostitis. Clinical diagnosis is unreliable. CECS and bone stress injury or traction periostitis can occur separately or together.

  12. Introduction to Pediatric Sepsis.

    PubMed

    Wheeler, Derek S

    2011-10-07

    Sepsis is a significant health problem in both critically ill children and adults. While the mortality rate from sepsis is much lower in children, sepsis is directly responsible for over 4,000 childhood deaths per year in the United States alone. At face value, this number suggests that more children die per year in the United States from sepsis as the primary cause than from cancer. Unfortunately, there are few studies on the epidemiology, pathophysiology, and management of sepsis in children. Moreover, extrapolation of adult data to critically ill children is probably not appropriate due to several key developmental differences in the host response to infection and response to therapy. Therefore, additional studies targeting sepsis in the pediatric population are urgently required.

  13. THE ENDOTHELIUM IN SEPSIS.

    PubMed

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

    2016-03-01

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

  14. Neutrophil Dysfunction in Sepsis

    PubMed Central

    Zhang, Fang; Liu, An-Lei; Gao, Shuang; Ma, Shui; Guo, Shu-Bin

    2016-01-01

    Objective: Sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection. In this article, we reviewed the correlation between neutrophil dysfunction and sepsis. Data Sources: Articles published up to May 31, 2016, were selected from the PubMed databases, with the keywords of “neutrophil function”, “neutrophil dysfunction”, and “sepsis”. Study Selection: Articles were obtained and reviewed to analyze the neutrophil function in infection and neutrophil dysfunction in sepsis. Results: We emphasized the diagnosis of sepsis and its limitations. Pathophysiological mechanisms involve a generalized circulatory, immune, coagulopathic, and/or neuroendocrine response to infection. Many studies focused on neutrophil burst or cytokines. Complement activation, impairment of neutrophil migration, and endothelial lesions are involved in this progress. Alterations of cytokines, chemokines, and other mediators contribute to neutrophil dysfunction in sepsis. Conclusions: Sepsis represents a severe derangement of the immune response to infection, resulting in neutrophil dysfunction. Neutrophil dysfunction promotes sepsis and even leads to organ failure. Mechanism studies, clinical practice, and strategies to interrupt dysregulated neutrophil function in sepsis are desperately needed. PMID:27824008

  15. THE ENDOTHELIUM IN SEPSIS

    PubMed Central

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

    2017-01-01

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

  16. Rapid diagnosis of sepsis

    PubMed Central

    Bloos, Frank; Reinhart, Konrad

    2014-01-01

    Fast and appropriate therapy is the cornerstone in the therapy of sepsis. However, the discrimination of sepsis from non-infectious causes of inflammation may be difficult. Biomarkers have been suggested to aid physicians in this decision. There is currently no biochemical technique available which alone allows a rapid and reliable discrimination between sepsis and non-infectious inflammation. Procalcitonin (PCT) is currently the most investigated biomarker for this purpose. C-reactive protein and interleukin 6 perform inferior to PCT in most studies and their value in diagnosing sepsis is not defined. All biomarkers including PCT are also released after various non-infectious inflammatory impacts. This shortcoming needs to be taken into account when biomarkers are used to aid the physician in the diagnosis of sepsis. Polymerase chain reaction (PCR) based pathogen detection may improve time to adequate therapy but cannot rule out the presence of infection when negative. PMID:24335467

  17. Implementing sepsis bundles

    PubMed Central

    Jozwiak, Mathieu; Monnet, Xavier

    2016-01-01

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

  18. Biomarkers of sepsis.

    PubMed

    Faix, James D

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate's effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high.

  19. The Microcirculation in Sepsis

    PubMed Central

    Tyagi, Asha; Sethi, Ashok Kumar; Girotra, Gautam; Mohta, Medha

    2009-01-01

    Summary Sepsis is a leading cause of mortality in critically ill patients. The pathophysiology of sepsis involves a highly complex and integrated response, including the activation of various cell types, inflammatory mediators, and the haemostatic system. Recent evidence suggests an emerging role of the microcirculation in sepsis, necessitating a shift in our locus away Irom the macrohaemodynamics to ill icrohaemodynanmics in a septic patient. This review article provides a brief overview of the microcirculation, its assessment techniques, and specific therapies to resuscitate the microhaemodynamics. PMID:20640135

  20. Neutrophil paralysis in sepsis.

    PubMed

    Alves-Filho, José C; Spiller, Fernando; Cunha, Fernando Q

    2010-09-01

    Sepsis develops when the initial host response is unable to contain the primary infection, resulting in widespread inflammation and multiple organ dysfunction. The impairment of neutrophil migration into the infection site, also termed neutrophil paralysis, is a critical hallmark of sepsis, which is directly related to the severity of the disease. Although the precise mechanism of this phenomenon is not fully understood, there has been much advancement in the understanding of this field. In this review, we highlight the recent insights into the molecular mechanisms of neutrophil paralysis during sepsis.

  1. Prehospital Sepsis Care.

    PubMed

    Jones, Jerrilyn; Lawner, Benjamin J

    2017-02-01

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

  2. Vitamin D and sepsis

    PubMed Central

    Kempker, Jordan A.; Han, Jenny E.; Tangpricha, Vin; Ziegler, Thomas R.; Martin, Greg S.

    2012-01-01

    Vitamin D insufficiency and sepsis are both highly prevalent worldwide problems and this article reviews the emerging science that is defining the intersections of these conditions. The importance of vitamin D’s role in skeletal health has long been understood but recent evidence is beginning to highlight its role in the functioning of other physiologic systems of the body. Basic science data reveal its integral role in local immune responses to pathogens and the systemic inflammatory pathways of sepsis. Furthermore, clinical scientists have found associations with respiratory infections, critical illness and sepsis but the causal relationship and its clinical impact have yet to be clearly defined. The article ends with speculations on the connections between racial disparities and seasonal differences in sepsis and vitamin D insufficiency. PMID:22928065

  3. Sepsis Questions and Answers

    MedlinePlus

    ... associated with infections of the lungs (e.g., pneumonia), urinary tract (e.g., kidney), skin, and gut. Staphylococcus aureus ( staph ), Escherichia coli ( E. coli ), and some types of Streptococcus (strep) are common germs that can cause sepsis. ...

  4. Artificial Limbs

    MedlinePlus

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

  5. Neurologic complications of sepsis.

    PubMed

    Schmutzhard, E; Pfausler, B

    2017-01-01

    Over the past decades, the incidence of sepsis and resultant neurologic sequelae has increased, both in industrialized and low- or middle-income countries, by approximately 5% per year. Up to 300 patients per 100 000 population per year are reported to suffer from sepsis, severe sepsis, and septic shock. Mortality is up to 30%, depending on the precision of diagnostic criteria. The increasing incidence of sepsis is partially explained by demographic changes in society, with aging, increasing numbers of immunocompromised patients, dissemination of multiresistant pathogens, and greater availability of supportive medical care in both industrialized and middle-income countries. This results in more septic patients being admitted to intensive care units. Septic encephalopathy is a manifestation especially of severe sepsis and septic shock where the neurologist plays a crucial role in diagnosis and management. It is well known that timely treatment of sepsis improves outcome and that septic encephalopathy may precede other signs and symptoms. Particularly in the elderly and immunocompromised patient, the brain may be the first organ to show signs of failure. The neurologist diagnosing early septic encephalopathy may therefore contribute to the optimal management of septic patients. The brain is not only an organ failing in sepsis (a "sepsis victim" - as with other organs), but it also overwhelmingly influences all inflammatory processes on a variety of pathophysiologic levels, thus contributing to the initiation and propagation of septic processes. Therefore, the best possible pathophysiologic understanding of septic encephalopathy is essential for its management, and the earliest possible therapy is crucial to prevent the evolution of septic encephalopathy, brain failure, and poor prognosis.

  6. [Severe sepsis and septic shock].

    PubMed

    Tønnesen, Else; Larsen, Kim

    2014-07-07

    Sepsis, severe sepsis and septic shock are syndromes. The incidence of sepsis is as high as 35% and with mortality rates in the intensive care unit from 27% to 54% in sepsis and septic shock, respectively. Many new treatments have been tested but only few have been implemented in clinical practise. The treatment of severe sepsis and septic shock is based on the Surviving Sepsis Campaign guidelines developed by an international expert panel. Early diagnosis, optimization of haemodynamics, rapid identification of focus and adequate antibiotic treatment are the most important strategies.

  7. Sepsis-associated encephalopathy.

    PubMed

    Cotena, Simona; Piazza, Ornella

    2012-01-01

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

  8. Sepsis: An update in management.

    PubMed

    Galen, Benjamin T; Sankey, Christopher

    2015-11-01

    Hospitalists are a critical link in providing evidence-based care for patients with sepsis across the disease spectrum, from early recognition to recovery. The past decade of sepsis research has led to significant findings that will change clinical practice for hospital medicine practitioners. Although the incidence of severe sepsis in the United States has continued to rise, in-hospital mortality has declined. Management of the spectrum of sepsis disorders is no longer restricted to the intensive care unit (ICU). This review article will provide an update in the management of sepsis for hospitalists based on recently published pivotal studies. The expanding evidence base in sepsis includes early goal-directed therapy/clinical endpoints/sepsis bundles, antibiotics and source control, volume resuscitation, ICU considerations (including the use of insulin and corticosteroids), mortality/complications, and the newly recognized condition of "sepsis survivorship".

  9. Mitochondrial Function in Sepsis

    PubMed Central

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

    2015-01-01

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

  10. Essentials of sepsis management.

    PubMed

    Green, John M

    2015-04-01

    Despite remarkable advances in the knowledge of infection and human response to it, sepsis continues to be one of the most common challenges surgeons and critical care providers face. Surgeons confront the problem of infection every day, in treating established infections or reacting to a consequence of surgical intervention. Infections after surgery continue to be a problem despite massive efforts to prevent them. Patients rely on the surgeon's ability to recognize infection and treat it. Also, preventing nosocomial infection and antibiotic resistance is a primary responsibility. This article describes diagnostic and therapeutic measures for sepsis in the perioperative surgical patient.

  11. 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

  12. Sepsis Associated Encephalopathy.

    PubMed

    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.

  13. Defining Neonatal Sepsis

    PubMed Central

    Wynn, James L.

    2016-01-01

    Purpose of the review Although infection rates have modestly decreased in the neonatal intensive care unit (NICU) as a result of ongoing quality improvement measures, neonatal sepsis remains a frequent and devastating problem among hospitalized preterm neonates. Despite multiple attempts to address this unmet need, there have been minimal advances in clinical management, outcomes, and accuracy of diagnostic testing options over the last three decades. One strong contributor to a lack of medical progress is a variable case definition of disease. The inability to agree on a precise definition greatly reduces the likelihood of aligning findings from epidemiologists, clinicians, and researchers, which, in turn, severely hinders progress towards improving outcomes. Recent findings Pediatric consensus definitions for sepsis are not accurate in term infants and are not appropriate for preterm infants. In contrast to the defined multi-stage criteria for other devastating diseases encountered in the NICU (e.g., bronchopulmonary dysplasia), there is significant variability in the criteria used by investigators to substantiate the diagnosis of neonatal sepsis. Summary The lack of an accepted consensus definition for neonatal sepsis impedes our efforts towards improved diagnostic and prognostic options as well as accurate outcomes information for this vulnerable population. PMID:26766602

  14. Limb Loss

    MedlinePlus

    ... limb. Learning how to use it takes time. Physical therapy can help you adapt. Recovery from the loss of a limb can be hard. Sadness, anger, and frustration are common. If you are having a tough time, talk to your doctor. Treatment with medicine or counseling can help.

  15. 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

  16. Sepsis and the heart.

    PubMed

    Hunter, J D; Doddi, M

    2010-01-01

    Septic shock, the most severe complication of sepsis, accounts for approximately 10% of all admissions to intensive care. Our understanding of its complex pathophysiology remains incomplete but clearly involves stimulation of the immune system with subsequent inflammation and microvascular dysfunction. Cardiovascular dysfunction is pronounced and characterized by elements of hypovolaemic, cytotoxic, and distributive shock. In addition, significant myocardial depression is commonly observed. This septic cardiomyopathy is characterized by biventricular impairment of intrinsic myocardial contractility, with a subsequent reduction in left ventricular (LV) ejection fraction and LV stroke work index. This review details the myocardial dysfunction observed in adult septic shock, and discusses the underlying pathophysiology. The utility of using the regulatory protein troponin for the detection of myocardial dysfunction is also considered. Finally, options for the management of sepsis-induced LV hypokinesia are discussed, including the use of levosimendan.

  17. Defining and Diagnosing Sepsis.

    PubMed

    Scott, Michael C

    2017-02-01

    Sepsis is a heterogeneous clinical syndrome that encompasses infections of many different types and severity. Not surprisingly, it has confounded most attempts to apply a single definition, which has also limited the ability to develop a set of reliable diagnostic criteria. It is perhaps best defined as the different clinical syndromes produced by an immune response to infection that causes harm to the body beyond that of the local effects of the infection.

  18. Coagulation and sepsis.

    PubMed

    Levi, Marcel; van der Poll, Tom

    2017-01-01

    Severe sepsis is almost invariably associated with systemic activation of coagulation. There is ample evidence that demonstrates a wide-ranging cross-talk between hemostasis and inflammation, which is probably implicated in the pathogenesis of organ dysfunction in patients with sepsis. Inflammation not only leads to initiation and propagation of coagulation activity, but coagulation also markedly influences inflammation. Molecular mechanisms that play a role in inflammation-induced effects on coagulation have been recognized in much detail. Pro-inflammatory cells and cyto- and chemokines can activate the coagulation system and downregulate crucial physiological anticoagulant mechanisms. Initiation of coagulation activation and consequent thrombin generation is caused by expression of tissue factor on activated monocytes and endothelial cells and is ineffectually offset by tissue factor pathway inhibitor. At the same time, endothelial-associated anticoagulant pathways, in particular the protein C system, is impaired by pro-inflammatory cytokines. Also, fibrin removal is severely obstructed by inactivation of the endogenous fibrinolytic system, mainly as a result of upregulation of its principal inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Increased fibrin generation and impaired break down lead to deposition of (micro)vascular clots, which may contribute to tissue ischemia and ensuing organ dysfunction. The foundation of the management of coagulation in sepsis is the explicit and thorough treatment of the underlying disorder by antibiotic treatment and source control measures. Adjunctive strategies focused at the impairment of coagulation, including anticoagulants and restoration of physiological anticoagulant mechanisms, may supposedly be indicated and have been found advantageous in experimental and initial clinical trials.

  19. Sepsis and septic shock.

    PubMed

    Maloney, Patrick J

    2013-08-01

    Early recognition of sepsis and septic shock in children relies on obtaining an attentive clinical history, accurate vital signs, and a physical examination focused on mental status, work of breathing, and circulatory status. Laboratory tests may support the diagnosis but are not reliable in isolation. The goal of septic shock management is reversal of tissue hypoperfusion. The therapeutic end point is shock reversal. Mortality is significantly better among children when managed appropriately. Every physician who cares for children must strive to have a high level of suspicion and keen clinical acumen for recognizing the rare but potentially seriously ill child.

  20. Sepsis in Special Populations.

    PubMed

    Borloz, Matthew P; Hamden, Khalief E

    2017-02-01

    Sepsis is recognized by the presence of physiologic and laboratory changes that reflect the inflammatory response to infection on cellular and systemic levels. Comorbid conditions, such as cirrhosis, end-stage renal disease, and obesity, alter patients' susceptibility to infection and their response to it once present. Baseline changes in vital signs and chronic medications often mask clues to the severity of illness. The physiologic, hematologic, and biochemical adjustments that accompany pregnancy and the puerperium introduce similar challenges. Emergency providers must remain vigilant for subtle alterations in the expected baseline for these conditions to arrive at appropriate management decisions.

  1. The role of the liver in sepsis.

    PubMed

    Yan, Jun; Li, Song; Li, Shulin

    2014-01-01

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

  2. Gender differences in sepsis

    PubMed Central

    Angele, Martin K; Pratschke, Sebastian; Hubbard, William J; Chaudry, Irshad H

    2014-01-01

    During sepsis, a complex network of cytokine, immune, and endothelial cell interactions occur and disturbances in the microcirculation cause organ dysfunction or even failure leading to high mortality in those patients. In this respect, numerous experimental and clinical studies indicate sex-specific differences in infectious diseases and sepsis. Female gender has been demonstrated to be protective under such conditions, whereas male gender may be deleterious due to a diminished cell-mediated immune response and cardiovascular functions. Male sex hormones, i.e., androgens, have been shown to be suppressive on cell-mediated immune responses. In contrast, female sex hormones exhibit protective effects which may contribute to the natural advantages of females under septic conditions. Thus, the hormonal status has to be considered when treating septic patients. Therefore, potential therapies could be derived from this knowledge. In this respect, administration of female sex hormones (estrogens and their precursors) may exert beneficial effects. Alternatively, blockade of male sex hormone receptors could result in maintained immune responses under adverse circulatory conditions. Finally, administration of agents that influence enzymes synthesizing female sex hormones which attenuate the levels of pro-inflammatory agents might exert salutary effects in septic patients. Prospective patient studies are required for transferring those important experimental findings into the clinical arena. PMID:24193307

  3. Cytopathic hypoxia in sepsis.

    PubMed

    Fink, M

    1997-01-01

    Diminished availability of oxygen at the cellular level might account for organ dysfunction in sepsis. Although the classical forms of tissue hypoxia due to hypoxemia, anemia, or inadequate perfusion all might be important under some conditions, it seems increasingly likely that a fourth mechanism, namely cytopathic hypoxia, might play a role as well. The term cytopathic hypoxia is used to denote diminished production of adenosine triphosphate (ATP) despite normal (or even supranormal) PO2 values in the vicinity of mitochondria within cells. At least in theory, cytopathic hypoxia could be a consequence of several different (but mutually compatible) pathogenic mechanisms, including diminished delivery of a key substrate (e.g., pyruvate) into the mitochondrial tricarboxylic acid (TCA) cycle, inhibition of key mitochondrial enzymes involved in either the TCA cycle or the electron transport chain, activation of the enzyme, poly-(ADP)-ribosylpolymerase (PARP), or collapse of the protonic gradient across the inner mitochondrial membrane leading to uncoupling of oxidation (of NADH and FADH) from phosphorylation of ADP to form ATP. Tantalizing, but limited, data support the view that cytopathic hypoxia occurs in both animals and patients with sepsis or endotoxemia.

  4. Renal blood flow in sepsis

    PubMed Central

    Langenberg, Christoph; Bellomo, Rinaldo; May, Clive; Wan, Li; Egi, Moritoki; Morgera, Stanislao

    2005-01-01

    Introduction To assess changes in renal blood flow (RBF) in human and experimental sepsis, and to identify determinants of RBF. Method Using specific search terms we systematically interrogated two electronic reference libraries to identify experimental and human studies of sepsis and septic acute renal failure in which RBF was measured. In the retrieved studies, we assessed the influence of various factors on RBF during sepsis using statistical methods. Results We found no human studies in which RBF was measured with suitably accurate direct methods. Where it was measured in humans with sepsis, however, RBF was increased compared with normal. Of the 159 animal studies identified, 99 reported decreased RBF and 60 reported unchanged or increased RBF. The size of animal, technique of measurement, duration of measurement, method of induction of sepsis, and fluid administration had no effect on RBF. In contrast, on univariate analysis, state of consciousness of animals (P = 0.005), recovery after surgery (P < 0.001), haemodynamic pattern (hypodynamic or hyperdynamic state; P < 0.001) and cardiac output (P < 0.001) influenced RBF. However, multivariate analysis showed that only cardiac output remained an independent determinant of RBF (P < 0.001). Conclusion The impact of sepsis on RBF in humans is unknown. In experimental sepsis, RBF was reported to be decreased in two-thirds of studies (62 %) and unchanged or increased in one-third (38%). On univariate analysis, several factors not directly related to sepsis appear to influence RBF. However, multivariate analysis suggests that cardiac output has a dominant effect on RBF during sepsis, such that, in the presence of a decreased cardiac output, RBF is typically decreased, whereas in the presence of a preserved or increased cardiac output RBF is typically maintained or increased. PMID:16137349

  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. Fluid Resuscitation in Severe Sepsis.

    PubMed

    Loflin, Rob; Winters, Michael E

    2017-02-01

    Since its original description in 1832, fluid resuscitation has become the cornerstone of early and aggressive treatment of severe sepsis and septic shock. However, questions remain about optimal fluid composition, dose, and rate of administration for critically ill patients. This article reviews pertinent physiology of the circulatory system, pathogenesis of septic shock, and phases of sepsis resuscitation, and then focuses on the type, rate, and amount of fluid administration for severe sepsis and septic shock, so providers can choose the right fluid, for the right patient, at the right time.

  7. Understanding brain dysfunction in sepsis

    PubMed Central

    2013-01-01

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

  8. Neonatal Sepsis and Inflammatory Mediators

    PubMed Central

    Reis Machado, Juliana; Soave, Danilo Figueiredo; da Silva, Marcos Vinícius; de Menezes, Liliana Borges; Etchebehere, Renata Margarida; Monteiro, Maria Luiza Gonçalves dos Reis; Antônia dos Reis, Marlene; Corrêa, Rosana Rosa Miranda; Celes, Mara Rúbia Nunes

    2014-01-01

    Neonatal sepsis is a major cause of morbidity and mortality and its signs and symptoms are nonspecific, which makes the diagnosis difficult. The routinely used laboratory tests are not effective methods of analysis, as they are extremely nonspecific and often cause inappropriate use of antibiotics. Sepsis is the result of an infection associated with a systemic inflammatory response with production and release of a wide range of inflammatory mediators. Cytokines are potent inflammatory mediators and their serum levels are increased during infections, so changes from other inflammatory effector molecules may occur. Although proinflammatory and anti-inflammatory cytokines have been identified as probable markers of neonatal infection, in order to characterize the inflammatory response during sepsis, it is necessary to analyze a panel of cytokines and not only the measurement of individual cytokines. Measurements of inflammatory mediators bring new options for diagnosing and following up neonatal sepsis, thus enabling early treatment and, as a result, increased neonatal survival. By taking into account the magnitude of neonatal sepsis, the aim of this review is to address the role of cytokines in the pathogenesis of neonatal sepsis and its value as a diagnostic criterion. PMID:25614712

  9. Severe sepsis in older adults.

    PubMed

    Umberger, Reba; Callen, Bonnie; Brown, Mary Lynn

    2015-01-01

    Severe sepsis may be underrecognized in older adults. Therefore, the purpose of this article is to review special considerations related to early detection of severe sepsis in older adults. Normal organ changes attributed to aging may delay early detection of sepsis at the time when interventions have the greatest potential to improve patient outcomes. Systems are reviewed for changes. For example, the cardiovascular system may have a limited or absent compensatory response to inflammation after an infectious insult, and the febrile response and recruitment of white blood cells may be blunted because of immunosenescence in aging. Three of the 4 hallmark responses (temperature, heart rate, and white blood cell count) to systemic inflammation may be diminished in older adults as compared with younger adults. It is important to consider that older adults may not always manifest the typical systemic inflammatory response syndrome. Atypical signs such as confusion, decreased appetite, and unsteady gait may occur before sepsis related organ failure. Systemic inflammatory response syndrome criteria and a comparison of organ failure criteria were reviewed. Mortality rates in sepsis and severe sepsis remain high and are often complicated by multiple organ failures. As the numbers of older adults increase, early identification and prompt treatment is crucial in improving patient outcomes.

  10. Antibiotic use in neonatal sepsis.

    PubMed

    Yurdakök, M

    1998-01-01

    Neonatal sepsis is a life-threatening emergency and any delay in treatment may cause death. Initial signs of neonatal sepsis are slight and nonspecific. Therefore, in suspected sepsis, two or three days empirical antibiotic therapy should begin immediately after cultures have been obtained without awaiting the results. Antibiotics should be reevaluated when the results of the cultures and susceptibility tests are available. If the cultures are negative and the clinical findings are well, antibiotics should be stopped. Because of the nonspecific nature of neonatal sepsis, especially in small preterm infants, physicians continue antibiotics once started. If a baby has pneumonia or what appears to be sepsis, antibiotics should not be stopped, although cultures are negative. The duration of therapy depends on the initial response to the appropriate antibiotics but should be 10 to 14 days in most infants with sepsis and minimal or absent focal infection. In infants who developed sepsis during the first week of life, empirical therapy must cover group B streptococci, Enterobacteriaceae (especially E. coli) and Listeria monocytogenes. Penicillin or ampicillin plus an aminoglycoside is usually effective against all these organisms. Initial empirical antibiotic therapy for infants who developed sepsis beyond the first days of life must cover the organisms associated with early-onset sepsis as well as hospital-acquired pathogens such as staphylococci, enterococci and Pseudomonas aeruginosa. Penicillin or ampicillin and an aminoglycoside combination may also be used in the initial therapy of late-onset sepsis as in cases with early-onset sepsis. In nosocomial infections, netilmicin or amikacin should be preferred. In cases showing increased risk of staphylococcal infection (e.g. presence of vascular catheter) or Pseudomonas infection (e.g. presence of typical skin lesions), antistaphylococcal or anti-Pseudomonas agents may be preferred in the initial empirical therapy. In

  11. Sepsis-associated encephalopathy.

    PubMed

    Gofton, Teneille E; Young, G Bryan

    2012-10-01

    Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs secondary to infection in the body without overt CNS infection. SAE is frequently encountered in critically ill patients in intensive care units, and in up to 70% of patients with severe systemic infection. The severity of SAE can range from mild delirium to deep coma. Seizures and myoclonus are infrequent and cranial nerves are almost always spared, but most severe cases have an associated critical illness neuromyopathy. Development of SAE probably involves a number of mechanisms that are not mutually exclusive and vary from patient to patient. Substantial neurological and psychological morbidities often occur in survivors. Mortality is almost always due to multiorgan failure rather than neurological complications, and is almost 70% in patients with severe SAE. Further research into the pathophysiology, management and prevention of SAE is needed. This Review discusses the epidemiology and clinical presentation of SAE. Recent evidence for SAE pathophysiology is outlined and a diagnostic approach to patients with this syndrome is presented. Lastly, prognosis and management of SAE is discussed.

  12. 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

  13. Sepsis care: getting it right every time.

    PubMed

    2016-10-06

    In the UK, there are an estimated 150,000 cases of sepsis per year, resulting in 44,000 deaths. This equates to more deaths than from bowel, breast and prostate cancer combined according to the Sepsis Trust.

  14. Current epidemiology of sepsis in mainland China

    PubMed Central

    Liao, Xuelian; Du, Bin; Lu, Meizhu; Wu, Minming

    2016-01-01

    The disease burden of sepsis is a global issue. Most of the large-scale epidemiological investigations on sepsis have been carried out in developed countries. The population of 1.3 billion in mainland China accounts for approximately 1/5th of the whole world population. Thus, the knowledge of the incidence and mortality of sepsis in mainland China is vital before employing measures for its improvement. However, most of the epidemiological data of sepsis in mainland China was obtained from ICU settings, and thus lacks the population-based incidence and mortality of sepsis. In the present review, we summarized the limited literature encompassing the incidence, mortality, long-term outcome, and pathogens of sepsis in mainland China. Therefore, it might provide some valuable information regarding the sepsis disease burden and current issues in the management of sepsis in mainland China. PMID:27713882

  15. Established and novel biomarkers of sepsis.

    PubMed

    Faix, James D

    2011-04-01

    The increased incidence of sepsis, a systemic response to infection that occurs in some patients, has stimulated interest in identifying infected patients who are at risk and intervening early. When this condition progresses to severe sepsis (characterized by organ dysfunction), mortality is high. Hospitals that have implemented recommendations of the Surviving Sepsis Campaign have seen a reduction in mortality rate for hospital-acquired severe sepsis. They may reduce this further by focusing on new approaches to diagnosing sepsis, especially at an early stage. Sepsis is a complicated syndrome with many physiological derangements and many emerging laboratory markers of sepsis have been proposed as adjuncts to clinical evaluation. The list includes cytokines, acute phase proteins, neutrophil activation markers, markers of abnormal coagulation and, recently, markers of suppression of both the innate and adaptive immune response. The perfect biomarker would accurately identify patients at risk of developing severe sepsis and then guide targeted therapy.

  16. [Understanding the pathogenetic mechanisms of SIRS and sepsis and development of innovative therapies of sepsis].

    PubMed

    Aikawa, Naoki; Fujishima, Seitaro

    2004-12-01

    The concept of systemic inflammatory response syndrome (SIRS) was introduced in 1992 to define and objectively diagnose sepsis. Over the last decade, the definition of sepsis has been used for inclusion criteria of multicenter trials to develop innovative therapies of sepsis. With the recent understanding of the pathogenetic mechanisms of sepsis, many drugs have been tested, but only two drugs (activated protein C and neutrophil-elastase inhibitor) have been approved for clinical use in sepsis or SIRS. Further understanding of basic pathophysiology of SIRS and sepsis holds promise to develop a new therapeutic strategy to improve survival of patients with SIRS and sepsis.

  17. Association of fungal sepsis and galactosemia.

    PubMed

    Verma, Sanjay; Bharti, Bhavneet; Inusha, P

    2010-06-01

    Galactosemia is one of the rare inborn errors of metabolism, which if detected early can be treated effectively. Galactosemic infants have a significant increased risk of developing sepsis. E. coli sepsis is a known entity, and also an important cause of early mortality in these children. But fungal sepsis in these patients is rarely reported. Here is a case of 45 day-old child who presented with fungal sepsis, which on investigation turned out to be galactosemia.

  18. 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

  19. The inflammatory response in sepsis.

    PubMed

    Bosmann, Markus; Ward, Peter A

    2013-03-01

    The pathophysiology of sepsis and its accompanying systemic inflammatory response syndrome (SIRS) and the events that lead to multiorgan failure and death are poorly understood. It is known that, in septic humans and rodents, the development of SIRS is associated with a loss of the redox balance, but SIRS can also develop in noninfectious states. In addition, a hyperinflammatory state develops, together with impaired innate immune functions of phagocytes, immunosuppression, and complement activation, collectively leading to septic shock and lethality. Here, we discuss recent insights into the signaling pathways in immune and phagocytic cells that underlie sepsis and SIRS and consider how these might be targeted for therapeutic interventions to reverse or attenuate pathways that lead to lethality during sepsis.

  20. Sepsis associated encephalopathy (SAE): a review.

    PubMed

    Green, Rebecca; Scott, L Keith; Minagar, Alireza; Conrad, Steven

    2004-05-01

    Sepsis associated encephalopathy (SAE) is a poorly understood condition that is associated with severe sepsis and appears to have a negative influence on survival. The incidence of encephalopathy secondary to sepsis is unknown. Amino acid derangements, blood-brain barrier disruption, abnormal neurotransmitters, and direct CNS effect are possible causes of septic encephalopathy. Research has not defined the pathogenesis of SAE.

  1. Galactosemia presenting as recurrent sepsis.

    PubMed

    Rathi, Narendra; Rathi, Akanksha

    2011-12-01

    Galactosemia is a treatable metabolic disorder caused by the deficiency of enzyme galactose-1-phosphate uridyl transferase (GALT) and inherited as an autosomal recessive trait. A case of neonate manifesting with recurrent Escherichia coli sepsis is presented here which turned out to be a classic galactosemia. No other common presenting features were observed in this infant except cataract on slit lamp examination. To the best of our knowledge, there is no case of galactosemia reported in literature which presented with recurrent neonatal sepsis without hepatomegaly, hyperbilirubinemia, bleeding disorder, vomiting, diarrhea, failure to thrive, hypoglycemia, coagulopathy, hemolysis or renal tubular acidosis.

  2. Vasopressors and Inotropes in Sepsis.

    PubMed

    Stratton, Leeanne; Berlin, David A; Arbo, John E

    2017-02-01

    Vasopressor and inotropes are beneficial in shock states. Norepinephrine is considered the first-line vasopressor for patients with sepsis-associated hypotension. Dobutamine is considered the first-line inotrope in sepsis, and should be considered for patients with evidence of myocardial dysfunction or ongoing signs of hypoperfusion. Vasopressor and inotrope therapy has complex effects that are often difficult to predict; emergency providers should consider the physiology and clinical trial data. It is essential to continually reevaluate the patient to determine if the selected treatment is having the intended result.

  3. Sepsis and Septic Shock: Lingering Questions.

    PubMed

    Dumont, Tiffany; Francis-Frank, Lyndave; Chong, Josebelo; Balaan, Marvin R

    2016-01-01

    Sepsis and septic shock are major health conditions in the United States, with a high incidence and mortality. The Surviving Sepsis Campaign, which was formed in 2002, formulates guidelines for the management of severe sepsis and septic shock and has actually demonstrated a reduction in mortality with institution of "sepsis bundles." Despite this, some elements of the guidelines have been questioned, and recent data suggest that strict compliance with bundles and protocols may not be necessary. Still, prompt recognition and treatment of sepsis and septic shock remain of utmost importance.

  4. [Molecular biology and immunopathogenetic mechanisms of sepsis].

    PubMed

    Průcha, M

    2009-01-01

    Sepsis, the systemic inflammatory response to infection, causes high mortality in patients in non-coronary units of intensive care. The most important characteristic of sepsis is the interaction between two subjects, the macro and the microorganism, associated with the dysfunction of innate and adaptive immunity. Sepsis is understood more as a dynamic syndrome characterized by many phenomenona which are often antagonistic. The inflammation, characterizing sepsis, does not act as a primary physiological compensatory mechanism and rather oscillates between the phase of hyperinflammatory response and anergy or immunoparalysis. The elucidation of the pathogenesis of sepsis is linked to the understanding of immunopathogenetic mechanisms, which characterize the interaction between the macro and microorganisms.

  5. What is next in sepsis: current trials in sepsis.

    PubMed

    Artigas, Antonio; Niederman, Michael S; Torres, Antoni; Carlet, Jean

    2012-08-01

    International experts reviewed and updated the most recent and relevant scientific advances on severe sepsis during the 17th International Symposium on Infections in the Critically Ill Patients in Barcelona (Spain) in February 2012. All new pharmacological therapeutic strategies have failed to demonstrate a survival benefit. Despite the large variability among countries and hospitals, the improvement of standard care according to the Surviving Sepsis campaign recommendations reduced the 28-day mortality to 24%. These results may have implications for future clinical trials in which much larger samples sizes of patients at high risk of death will be necessary. The identification of novel proinflammatory endogeneous signals and pathways may lead to the discovery of new drugs to reduce inflammatory reactions and end-organ dysfunction in critically ill patients with sepsis. Extracorporeal blood purification stem or progenitor cells have received increasing interest for the treatment of inflammation and organ injury. A better understanding of how these therapies work is essential and its benefit should be confirmed in future prospective randomized studies.

  6. End Points of Sepsis Resuscitation.

    PubMed

    Greenwood, John C; Orloski, Clinton J

    2017-02-01

    Resuscitation goals for the patient with sepsis and septic shock are to return the patient to a physiologic state that promotes adequate end-organ perfusion along with matching metabolic supply and demand. Ideal resuscitation end points should assess the adequacy of tissue oxygen delivery and oxygen consumption, and be quantifiable and reproducible. Despite years of research, a single resuscitation end point to assess adequacy of resuscitation has yet to be found. Thus, the clinician must rely on multiple end points to assess the patient's overall response to therapy. This review will discuss the role and limitations of central venous pressure (CVP), mean arterial pressure (MAP), and cardiac output/index as macrocirculatory resuscitation targets along with lactate, central venous oxygen saturation (ScvO2), central venous-arterial CO2 gradient, urine output, and capillary refill time as microcirculatory resuscitation endpoints in patients with sepsis.

  7. 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

  8. Sepsis and Acute Kidney Injury.

    PubMed

    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

    2014-12-01

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

  9. Sepsis and Acute Kidney Injury

    PubMed Central

    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

    2014-01-01

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

  10. 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.

  11. [Sepsis: a new look at the problem].

    PubMed

    Beloborodova, N V

    2013-01-01

    The recent proceedings of congresses and forums on sepsis were used to write this review. The available definitions of sepsis and ideas on its etiology and pathogenesis are critically analyzed. There is information on new concepts of sepsis and data on a search for new targets, diagnostic and therapeutic approaches, and biomarkers. It is hypothesized that there is a mechanism of action of bacteria on mitochondrial dysfunction and human hormonal regulation with low-molecular weight exometabolites, namely aromatic microbial metabolites.

  12. Skeletal limb abnormalities

    MedlinePlus

    ... medlineplus.gov/ency/article/003170.htm Skeletal limb abnormalities To use the sharing features on this page, please enable JavaScript. Skeletal limb abnormalities refers to a variety of bone structure problems ...

  13. Critical Limb Ischemia (CLI)

    MedlinePlus

    ... High blood pressure Family history of vascular disease Warning Signs You may have critical limb ischemia if ... blood flow to the limb. Other treatments include laser atherectomy, where small bits of plaque are vaporized ...

  14. Mechanical Ventilation in Sepsis: A Reappraisal.

    PubMed

    Zampieri, Fernando G; Mazza, Bruno

    2017-01-01

    Sepsis is the main cause of close to 70% of all cases of acute respiratory distress syndromes (ARDS). In addition, sepsis increases susceptibility to ventilator-induced lung injury. Therefore, the development of a ventilatory strategy that can achieve adequate oxygenation without injuring the lungs is highly sought after for patients with acute infection and represents an important therapeutic window to improve patient care. Suboptimal ventilatory settings cannot only harm the lung, but may also contribute to the cascade of organ failure in sepsis due to organ crosstalk.Despite the prominent role of sepsis as a cause for lung injury, most of the studies that addressed mechanical ventilation strategies in ARDS did not specifically assess sepsis-related ARDS patients. Consequently, most of the recommendations regarding mechanical ventilation in sepsis patients are derived from ARDS trials that included multiple clinical diagnoses. While there have been important improvements in general ventilatory management that should apply to all critically ill patients, sepsis-related lung injury might still have particularities that could influence bedside management.After revisiting the interplay between sepsis and ventilation-induced lung injury, this review will reappraise the evidence for the major components of the lung protective ventilation strategy, emphasizing the particularities of sepsis-related acute lung injury.

  15. Antimicrobial Stewardship in the Management of Sepsis.

    PubMed

    Pulia, Michael S; Redwood, Robert; Sharp, Brian

    2017-02-01

    Sepsis represents a unique clinical dilemma with regard to antimicrobial stewardship. The standard approach to suspected sepsis in the emergency department centers on fluid resuscitation and timely broad-spectrum antimicrobials. The lack of gold standard diagnostics and evolving definitions for sepsis introduce a significant degree of diagnostic uncertainty that may raise the potential for inappropriate antimicrobial prescribing. Intervention bundles that combine traditional quality improvement strategies with emerging electronic health record-based clinical decision support tools and rapid molecular diagnostics represent the most promising approach to enhancing antimicrobial stewardship in the management of suspected sepsis in the emergency department.

  16. Ready for Prime Time? Biomarkers in Sepsis.

    PubMed

    Long, Brit; Koyfman, Alex

    2017-02-01

    Sepsis is a common condition managed in the emergency department. Current diagnosis relies on physiologic criteria and suspicion of a source of infection using history, physical examination, laboratory studies, and imaging studies. The infection triggers a host response with the aim to destroy the pathogen, and this response can be measured. A reliable biomarker for sepsis should assist with earlier diagnosis, improve risk stratification, or improve clinical decision making. Current biomarkers for sepsis include lactate, troponin, and procalcitonin. This article discusses the use of lactate, procalcitonin, troponin, and novel biomarkers for use in sepsis.

  17. Monocyte Profiles in Critically Ill Patients With Pseudomonas Aeruginosa Sepsis

    ClinicalTrials.gov

    2017-02-02

    Pseudomonas Infections; Pseudomonas Septicemia; Pseudomonas; Pneumonia; Pseudomonal Bacteraemia; Pseudomonas Urinary Tract Infection; Pseudomonas Gastrointestinal Tract Infection; Sepsis; Sepsis, Severe; Critically Ill

  18. Neonatal sepsis-- a global problem: an overview.

    PubMed

    Afroza, S

    2006-01-01

    Neonatal sepsis is one of the major health problems throughout the world. Every year an estimated 30 million newborns acquire infection and 1-2 million of these die. The present review provides updates regarding neonatal sepsis to help paediatricians to protect the newborn from this deadly problem. The onset of sepsis within first 48 hours of life (early onset sepsis) is frequently associated with pre and perinatal predisposing factors while onset after 48-72 hours of life (late onset sepsis) frequently reflects infection acquired nosocomially. Some literatures say that early onset disease presents in the first 5-7 days of life. Klebsiella pneumoniae is the leading pathogen causing neonatal sepsis in Bangladesh and neighbouring countries. Among many risk factors the single most important neonatal risk factor is low birth weight. Other main risk factors are invassive procedures in the postnatal period and inadequate hand washing before and after handling babies. Sepsis score is a useful method for early and rapid diagnosis of neonatal sepsis which was developed by Tollner U in 1982. Antibiotics should be given to most of the neonates suspected of infection. Ampicillin and gentamicin are the first drug of choice. In Bangladesh context sepsis score may be used as a good parameter for the early and rapid diagnosis of sepsis and that will guide the treatment plan. Clean and safe delivery, early and exclusive breastfeeding, strict postnatal cleanliness following adequate handwashing and aseptic technique during invasive procedure might reduce the incidence of neonatal sepsis. Prompt use of antibiotic according to standard policy is warranted to save the newborn lives from septicaemia.

  19. Pelvic sepsis after stapled hemorrhoidopexy

    PubMed Central

    van Wensen, Remco JA; van Leuken, Maarten H; Bosscha, Koop

    2008-01-01

    Stapled hemorrhoidopexy is a surgical procedure used worldwide for the treatment of grade III and IV hemorrhoids in all age groups. However, life-threatening complications occur occasionally. The following case report describes the development of pelvic sepsis after stapled hemorrhoidopexy. A literature review of techniques used to manage major septic complications after stapled hemorrhoidopexy was performed. There is no standardized treatment currently available. Stapled hemorrhoidopexy is a safe, effective and time-efficient procedure in the hands of experienced colorectal surgeons. PMID:18855996

  20. Burn sepsis and burn toxin

    PubMed Central

    Allgöwer, Martin; Städtler, Karl; Schoenenberger, Guido A

    1974-01-01

    The salient steps of a 20-year programme of research into the nature of burn disease are described. By burn disease we mean the late mortality and morbidity following burns. We have isolated a burn toxin which is derived from a thermal polymerization of cell membrane lipoproteins within the dermis and have studied its influence on the effects of sepsis. We have also used it in the development of active and passive immunization therapy of severe burns. ImagesFig. 2Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9 PMID:4429330

  1. Sepsis-associated encephalopathy: not just delirium

    PubMed Central

    Zampieri, Fernando Godinho; Park, Marcelo; Machado, Fabio Santana; Azevedo, Luciano Cesar Pontes

    2011-01-01

    Sepsis is a major cause of mortality and morbidity in intensive care units. Organ dysfunction is triggered by inflammatory insults and tissue hypoperfusion. The brain plays a pivotal role in sepsis, acting as both a mediator of the immune response and a target for the pathologic process. The measurement of brain dysfunction is difficult because there are no specific biomarkers of neuronal injury, and bedside evaluation of cognitive performance is difficult in an intensive care unit. Although sepsis-associated encephalopathy was described decades ago, it has only recently been subjected to scientific scrutiny and is not yet completely understood. The pathophysiology of sepsis-associated encephalopathy involves direct cellular damage to the brain, mitochondrial and endothelial dysfunction and disturbances in neurotransmission. This review describes the most recent findings in the pathophysiology, diagnosis, and management of sepsis-associated encephalopathy and focuses on its many presentations. PMID:22012058

  2. Abnormal heart rate characteristics preceding neonatal sepsis and sepsis-like illness.

    PubMed

    Griffin, M Pamela; O'Shea, T Michael; Bissonette, Eric A; Harrell, Frank E; Lake, Douglas E; Moorman, J Randall

    2003-06-01

    Late-onset neonatal sepsis is a significant cause of morbidity and mortality, and early detection could prove beneficial. Previously, we found that abnormal heart rate characteristics (HRC) of reduced variability and transient decelerations occurred early in the course of neonatal sepsis and sepsis-like illness in infants in a single neonatal intensive care unit (NICU). We hypothesized that this finding can be generalized to other NICUs. We prospectively collected clinical data and continuously measured RR intervals in all infants in two NICUs who stayed for >7 d. We defined episodes of sepsis and sepsis-like illness as acute clinical deteriorations that prompted physicians to obtain blood cultures and start antibiotics. A predictive statistical model yielding an HRC index was developed on a derivation cohort of 316 neonates in the University of Virginia NICU and then applied to the validation cohort of 317 neonates in the Wake Forest University NICU. In the derivation cohort, there were 155 episodes of sepsis and sepsis-like illness in 101 infants, and in the validation cohort, there were 118 episodes in 93 infants. In the validation cohort, the HRC index 1) showed highly significant association with impending sepsis and sepsis-like illness (receiver operator characteristic area 0.75, p < 0.001) and 2) added significantly to the demographic information of birth weight, gestational age, and days of postnatal age in predicting sepsis and sepsis-like illness (p < 0.001). Continuous HRC monitoring is a generally valid and potentially useful noninvasive tool in the early diagnosis of neonatal sepsis and sepsis-like illness.

  3. Sepsis

    MedlinePlus

    ... Bones (common in children) Bowel (usually seen with peritonitis ) Kidneys (upper urinary tract infection , pyelonephritis or urosepsis) ... More Avian influenza Cellulitis Confusion Intravenous Meningitis Osteomyelitis Peritonitis Pneumonia - adults (community acquired) Septic shock Shock Urinary ...

  4. Sepsis as a model of SIRS.

    PubMed

    Bhatia, Madhav; He, Min; Zhang, Huili; Moochhala, Shabbir

    2009-01-01

    Sepsis describes a complex clinical syndrome that results from the host inability to regulate the inflammatory response against infection. Despite more than 20 years of extensive study, sepsis and excessive systemic inflammatory response syndrome (SIRS) are still the leading cause of death in intensive care units. The clinical study of sepsis and new therapeutics remains challenging due to the complexity of this disease. Therefore, many animal models have been employed to investigate the pathogenesis of sepsis and to preliminarily test potential therapeutics. However, so far, most therapeutics that have shown promising results in animal models failed in human clinical trials. In this chapter we will present an overview of different experimental animal models of sepsis and compare their advantages and disadvantage. The studies in animal models have greatly improved our understanding about the inflammatory mediators in sepsis. In this chapter we will also highlight the roles of several critical mediators including TNF-a , IL-1b , IL-6, chemokines, substance P, hydrogen sulfide and activated protein C in animal models of sepsis as well as in clinical studies.

  5. Five additions to the list of Sepsidae Diptera for Vietnam: Perochaeta cuirassa sp. n., Perochaeta lobo sp. n., Sepsis spura sp. n., Sepsis sepsi Ozerov, 2003 and Sepsis monostigma Thompson, 1869

    PubMed Central

    Ang, Yuchen; Meier, Rudolf

    2010-01-01

    Abstract A recent collecting trip to Vietnam yielded three new species and two new records of Sepsidae (Diptera) for the country. Here we describe two new species in the species-poor genus Perochaeta (Perochaeta cuirassa sp. n. andPerochaeta lobo sp. n.) and one to the largest sepsid genus Sepsis (Sepsis spura sp. n.) which is also found in Sumatra and Sulawesi. Two additional Sepsis species are new records for Vietnam (Sepsis sepsi Ozerov, 2003; Sepsis monostigma Thompson, 1869). We conclude with a discussion of the distribution of Perochaeta and the three Sepsis species. PMID:21594042

  6. [Model of meningococcal sepsis in mice].

    PubMed

    Krasnoproshina, L I; Ermakova, L G; Belova, T N; Filippov, Iu V; Efimov, D D

    1978-11-01

    The authors studied a possibility of obtaining experimental meningococcus sepsis model on mice. The use of cyclophosphane, iron compounds, yolk medium produced no significant organism. When 4--5% mucine was injected intraperitoneally together with meningococcus culture mice died with sepsis phenomena. Differences were revealed in the sensitivity of linear and mongrel mice to meningococcus infection--AKR mice proved to be more sensitive. At the same time it was found that mongrel mice weighing from 10 to 12 g could be used to induce meningococcus sepsis.

  7. Where Sepsis and Antimicrobial Resistance Countermeasures Converge

    PubMed Central

    Inglis, Timothy J. J.; Urosevic, Nadia

    2017-01-01

    The United Nations General Assembly debate on antimicrobial resistance (AMR) recognizes the global significance of AMR. Much work needs to be done on technology capability and capacity to convert the strategic intent of the debate into operational plans and tangible outcomes. Enhancement of the biomedical science–clinician interface requires better exploitation of systems biology tools for in-laboratory and point of care methods that detect sepsis and characterize AMR. These need to link sepsis and AMR data with responsive, real-time surveillance. We propose an AMR sepsis register, similar in concept to a cancer registry, to aid coordination of AMR countermeasures. PMID:28220145

  8. Pitfalls in the Treatment of Sepsis.

    PubMed

    Peterson, Lars-Kristofer N; Chase, Karin

    2017-02-01

    Sepsis is a challenging, dynamic, pathophysiology requiring expertise in diagnosis and management. Controversy exists as to the most sensitive early indicators of sepsis and sepsis severity. Patients presenting to the emergency department often lack complete history or clinical data that would point to optimal management. Awareness of these potential knowledge gaps is important for the emergency provider managing the septic patient. Specific areas of management including the initiation and management of mechanical ventilation, the appropriate disposition of the patient, and consideration of transfer to higher levels of care are reviewed.

  9. [Identification of the patient with sepsis].

    PubMed

    Rossi, B; Piazza, C; Moraschini, F; Marchesi, G M; Fumagalli, R

    2004-05-01

    Sepsis may be defined as a clinical syndrome caused by an organism's response to infection. The complex alterations triggered by the infection include inflammation and systemic coagulopathy in the absence of effective fibrinolysis. Possible manifestations vary in entity and severity, ranging from systemic inflammatory response syndrome (SIRS) to septic shock and multiorgan dysfunction syndrome (MODS). The nurse can play a fundamental role in the timely recognition of SIRS and in the early identification of the onset of signs of organ damage. In this way, an additional aid to establishing diagnosis can be provided and targeted treatment instituted. Following a brief presentation of the pathophysiology and epidemiology of sepsis, the manifestations and attendant risks are described, the most appropriate monitoring methods and the main nursing tasks in treating sepsis are discussed. We present the results of our experience in identifying patients with sepsis through the application of selection criteria adopted from clinical studies on the use of activated protein C.

  10. Understanding sepsis: from SIRS to septic shock.

    PubMed

    Hynes-Gay, Patricia; Lalla, Patti; Leo, Maria; Merrill-Bell, Audrey; Nicholson, Marjorie; Villaruel, Elizabeth

    2002-01-01

    Sepsis remains the leading cause of death in non-coronary ICU patients, despite improvements in supportive treatment modalities such as antimicrobial drugs and ventilation therapy. Further, the incidence of sepsis is projected to increase in years to come, related to factors including a rise in immunosuppressed patient populations and more widespread use of invasive lines and procedures. In this article, the authors seek to advance nurses' understanding of sepsis by reviewing the SIRS to septic shock paradigm and using a case study to illustrate how a patient progressed along the continuum. The role of the critical care nurse is an important aspect of the care of these patients. Early identification of patients at risk for, or who are developing, sepsis is crucial in order to improve patient outcomes.

  11. Staghorn calculus endotoxin expression in sepsis.

    PubMed

    McAleer, Irene M; Kaplan, George W; Bradley, John S; Carroll, Stephen F

    2002-04-01

    Staghorn calculi are infrequent and generally are infected stones. Struvite or apatite calculi are embedded with gram-negative bacteria, which can produce endotoxin. Sepsis syndrome may occur after surgical therapy or endoscopic manipulation of infected or staghorn calculi. Sepsis, which can occur despite perioperative antibiotic use, may be due to bacteremia or endotoxemia. We present a child with an infected staghorn calculus who developed overwhelming sepsis and died after percutaneous stone manipulation. Endotoxin assay of stone fragments demonstrated an extremely high level of endotoxin despite low colony bacterial culture growth. This is the first reported case in which endotoxin was demonstrated in stone fragments from a child who died of severe sepsis syndrome after percutaneous staghorn stone manipulation.

  12. Neuro-oxidative-nitrosative stress in sepsis.

    PubMed

    Berg, Ronan M G; Møller, Kirsten; Bailey, Damian M

    2011-07-01

    Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsis-induced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding brain parenchyma, due to failure of the local antioxidant systems. ROS/RNS cause structural membrane damage, induce inflammation, and scavenge nitric oxide (NO) to yield peroxynitrite (ONOO(-)). This activates the inducible NO synthase, which further compounds ONOO(-) formation. ROS/RNS cause mitochondrial dysfunction by inhibiting the mitochondrial electron transport chain and uncoupling oxidative phosphorylation, which ultimately leads to neuronal bioenergetic failure. Furthermore, in certain 'at risk' areas of the brain, free radicals may induce neuronal apoptosis. In the present review, we define a role for ROS/RNS-mediated neuronal bioenergetic failure and apoptosis as a primary mechanism underlying sepsis-associated encephalopathy and, in sepsis survivors, permanent cognitive deficits.

  13. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1988-03-15

    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.

  14. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1988-09-15

    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 and NO 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.

  15. 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

  16. Neonatal infectious diseases: evaluation of neonatal sepsis.

    PubMed

    Camacho-Gonzalez, Andres; Spearman, Paul W; Stoll, Barbara J

    2013-04-01

    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. This article reviews recent trends in epidemiology and provides an update on risk factors, diagnostic methods, and management of neonatal sepsis.

  17. 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

  18. Factors which affect mortality in neonatal sepsis

    PubMed Central

    Turhan, Esma Ebru; Gürsoy, Tuğba; Ovalı, Fahri

    2015-01-01

    Aim: Neonatal sepsis is an important cause of mortality and morbidity in newborns. The causative agents may be different in different units and may change in time. It was aimed to examine the microbiological agents leading to sepsis, clinical features and antibiotic resistances in babies with sepsis hospitalized in our unit in a two-year period. Material and Methods: The clinical features, microbiological and laboratory results, antibiotic resistance patterns and mortality rates of the newborns with sepsis followed up in our unit between 2010 and 2011 were examined in the patient record system. Results: 351 babies diagnosed with sepsis among 3219 patients hospitalized in the neonatal intensive care unit were included in the study. The mean gestational age was found to be 30.1±4.1 weeks, the mean birth weight was found to be 1417.4±759.1 g and the mean hospitalization time was found to be 43.6±34.4 days. Blood cultures were found to be positive in 167 (47.6%) patients, urine cultures were found to be positive in 6 (7.1%) patients and cerebrospinal fluid cultures were found to be positive in 34 (9.6%) cases. Candida grew in 5 patients (2 patients with early-onset sepsis and 3 patients with late-onset sepsis). The most common cause of sepsis was found to be staphylococci (coagulase negative staphylococcus was found in 65 patients (51%) and Staphylococcus aureus was found in 38 patients (39%). 49.6% (n=63) of the gram positive bacteriae and 60% (n=21) of the gram negative bacteriae were resistant to antibiotics. Six (7.1%) of the patients who were infected with these bacteriae were lost. In total 24 babies were lost because of sepsis. The bacteriae which caused to mortality with the highest rate included E. coli, coagulase negative staphylocicci, S. aureus and Klebsiella. Low birth weight, mechanical ventilation and parenteral nutrition were found to be significant risk factors in terms of mortality. Conclusions: Staphylococci were found to be the most common agents

  19. Improving Diagnosis of Sepsis After Burn Injury Using a Portable Sepsis Alert System

    DTIC Science & Technology

    2015-10-01

    the efficacy of the bedside decision support tool to detect burn sepsis using multicenter, prospective study, bedside laptops , and patient sensors...Task 4. Validate the efficacy of the bedside decision support tool to detect burn sepsis using multicenter, prospective study, bedside laptops , and

  20. Earth Limb Radiance Transformation.

    DTIC Science & Technology

    1981-03-02

    AD-A097 523 AEROSPACE CORP EL SEGUNDO CA CHEMISTRY AND PHYSICS LAB F/G 4/1 EARTH LIMB RADIANCE TRANSFORMATION (U) MAR AI S 4 YOUNG F0701-80 -C-0081... Earth Limb Radiance Trafisformation Prepared by S. J. YOUNG Chemistr and Physics Laboratory Laboratory Operations The Aerospace Corporation S.El...ITLEK (and Subtitle) TYPE OF REPORT & P53100 COVERED Earth Limb Radiance Transformation. ( Interim ./ / /TR-OJ081(697j7-g4)-l-- i7.Step hen J. Young

  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. Laboratory detection of sepsis: biomarkers and molecular approaches.

    PubMed

    Riedel, Stefan; Carroll, Karen C

    2013-09-01

    Sepsis, severe sepsis, and septic shock cause significant morbidity and mortality worldwide. Rapid diagnosis and therapeutic interventions are desirable to improve the overall mortality in patients with sepsis. However, gold standard laboratory diagnostic methods for sepsis, pose a significant challenge to rapid diagnosis of sepsis by physicians and laboratories. This article discusses the usefulness and potential of biomarkers and molecular test methods for a more rapid clinical and laboratory diagnosis of sepsis. Because new technologies are quickly emerging, physicians and laboratories must appreciate the key factors and characteristics that affect the clinical usefulness and diagnostic accuracy of these test methodologies.

  3. Sepsis-related hypertensive response: friend or foe?

    PubMed Central

    Saleh, Mohamed

    2014-01-01

    In daily practice acute arterial hypertension may occur during acute sepsis. No management guidelines concerning this issue figured in the latest sepsis campaign guidelines. Arterial hypertension occurring during sepsis could be an overlooked condition despite its potential haemodynamic harmful consequences. In this paper, a clinical study of acute hypertensive response related to sepsis is detailed. It shows that arterial hypertension, renal salt wasting and glomerular hyperfiltration can occur simultaneously during sepsis. Mechanisms and management options of sepsis-related arterial hypertensive response are also discussed. PMID:24855080

  4. 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.

  5. Burkholderia cepacia sepsis among neonates.

    PubMed

    Patra, Saikat; Bhat Y, Ramesh; Lewis, Leslie Edward; Purakayastha, Jayashree; Sivaramaraju, V Vamsi; Kalwaje E, Vandana; Mishra, Swathi

    2014-11-01

    Burkholderia cepacia is a rare cause of sepsis in newborns and its transmission involves human contact with heavily contaminated medical devices and disinfectants. The authors aimed to determine epidemiology, clinical features, antibiotic sensitivity pattern, complications and outcome of blood culture proven B. cepacia infections in 12 neonates. All neonates were outborn, 5 preterm and 7 term. B. cepacia was isolated from blood in all and concurrently from CSF in three neonates. Lethargy and respiratory distress (41.7 %) were major presenting features. Five newborns (41.7 %) required mechanical ventilation for 3-7 d. Highest bacterial susceptibility was observed for meropenem (100 %), followed by cefoperazone-sulbactam, piperacillin-tazobactam, sulfamethoxazole-trimethoprim (all 83 %), ceftazidime (75 %) and ciprofloxacin (42 %). Piperacillin-tazobactam, ciprofloxacin and cotrimoxazole either singly or in combination led to complete recovery of 11 (91.7 %) newborns; one developed hydrocephalus. Eight of nine infants who completed 6 mo follow up were normal. Prompt recognition and appropriate antibiotic therapy for B. cepacia infection results in complete recovery in majority.

  6. Immunological monitoring to prevent and treat sepsis

    PubMed Central

    2013-01-01

    The clinical, human and economic burden associated with sepsis is huge. Initiatives such as the Surviving Sepsis Campaign aim to effectively reduce risk of death from severe sepsis and septic shock. Nonetheless, although substantial benefits raised from the implementation of this campaign have been obtained, much work remains if we are to realise the full potential promised by this strategy. A deeper understanding of the processes leading to sepsis is necessary before we can design an effective suite of interventions. Dysregulation of the immune response to infection is acknowledged to contribute to the pathogenesis of the disease. Production of both proinflammatory and immunosuppressive cytokines is observed from the very first hours following diagnosis. In addition, hypogammaglobulinemia is often present in patients with septic shock. Moreover, levels of IgG, IgM and IgA at diagnosis correlate directly with survival. In turn, nonsurvivors have lower levels of C4 (a protein of the complement system) than the survivors. Natural killer cell counts and function also seem to have an important role in this disease. HLA-DR in the surface of monocytes and counts of CD4+CD25+ T-regulatory cells in blood could also be useful biomarkers for sepsis. At the genomic level, repression of networks corresponding to major histocompatibility complex antigen presentation is observed in septic shock. In consequence, cumulative evidence supports the potential role of immunological monitoring to guide measures to prevent or treat sepsis in a personalised and timely manner (early antibiotic administration, immunoglobulin replacement, immunomodulation). In conclusion, although diffuse and limited, current available information supports the development of large comprehensive studies aimed to urgently evaluate immunological monitoring as a tool to prevent sepsis, guide its treatment and, as a consequence, diminish the morbidity and mortality associated with this severe condition. PMID

  7. Immune cell phenotype and function in sepsis

    PubMed Central

    Rimmelé, Thomas; Payen, Didier; Cantaluppi, Vincenzo; Marshall, John; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A.

    2015-01-01

    Cells of the innate and adaptive immune systems play a critical role in the host response to sepsis. Moreover, their accessibility for sampling and their capacity to respond dynamically to an acute threat increases the possibility that leukocytes might serve as a measure of a systemic state of altered responsiveness in sepsis. The working group of the 14th Acute Dialysis Quality Initiative (ADQI) conference sought to obtain consensus on the characteristic functional and phenotypic changes in cells of the innate and adaptive immune system in the setting of sepsis. Techniques for the study of circulating leukocytes were also reviewed and the impact on cellular phenotypes and leukocyte function of non extracorporeal treatments and extracorporeal blood purification therapies proposed for sepsis was analyzed. A large number of alterations in the expression of distinct neutrophil and monocyte surface markers have been reported in septic patients. The most consistent alteration seen in septic neutrophils is their activation of a survival program that resists apoptotic death. Reduced expression of HLA-DR is a characteristic finding on septic monocytes but monocyte antimicrobial function does not appear to be significantly altered in sepsis. Regarding adaptive immunity, sepsis-induced apoptosis leads to lymphopenia in patients with septic shock and it involves all types of T cells (CD4, CD8 and Natural Killer) except T regulatory cells, thus favoring immunosuppression. Finally, numerous promising therapies targeting the host immune response to sepsis are under investigation. These potential treatments can have an effect on the number of immune cells, the proportion of cell subtypes and the cell function. PMID:26529661

  8. Phantom limb pain

    MedlinePlus

    ... Philadelphia, PA: Elsevier; 2015:chap 54. Nikolajsen L, Springer JS, Haroutiunian S. Phantom limb pain. In: Benzon HT, ... medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- ...

  9. Hyaluronan in limb morphogenesis.

    PubMed

    Li, Yingcui; Toole, Bryan P; Dealy, Caroline N; Kosher, Robert A

    2007-05-15

    Hyaluronan (HA) is a large glycosaminoglycan that is not only a structural component of extracellular matrices, but also interacts with cell surface receptors to promote cell proliferation, migration, and intracellular signaling. HA is a major component of the extracellular matrix of the distal subapical mesenchymal cells of the developing limb bud that are undergoing proliferation, directed migration, and patterning in response to the apical ectodermal ridge (AER), and has the functional potential to be involved in these processes. Here we show that the HA synthase Has2 is abundantly expressed by the distal subridge mesodermal cells of the chick limb bud and also by the AER itself. Has2 expression and HA production are downregulated in the proximal central core of the limb bud during the formation of the precartilage condensations of the skeletal elements, suggesting that downregulation of HA may be necessary for the close juxtaposition of cells and the resulting cell-cell interactions that trigger cartilage differentiation during condensation. Overexpression of Has2 in the mesoderm of the chick limb bud in vivo results in the formation of shortened and severely malformed limbs that lack one or more skeletal elements. Skeletal elements that do form in limbs overexpressing Has2 are reduced in length, exhibit abnormal morphology, and are positioned inappropriately. We also demonstrate that sustained HA production in micromass cultures of limb mesenchymal cells inhibits formation of precartilage condensations and subsequent chondrogenesis, indicating that downregulation of HA is indeed necessary for formation of the precartilage condensations that trigger cartilage differentiation. Taken together these results suggest involvement of HA in various aspects of limb morphogenesis.

  10. Limb regeneration: a new development?

    PubMed

    Nacu, Eugen; Tanaka, Elly M

    2011-01-01

    Salamander limb regeneration is a classical model of tissue morphogenesis and patterning. Through recent advances in cell labeling and molecular analysis, a more precise, mechanistic understanding of this process has started to emerge. Long-standing questions include to what extent limb regeneration recapitulates the events observed in mammalian limb development and to what extent are adult- or salamander- specific aspects deployed. Historically, researchers studying limb development and limb regeneration have proposed different models of pattern formation. Here we discuss recent data on limb regeneration and limb development to argue that although patterning mechanisms are likely to be similar, cell plasticity and signaling from nerves play regeneration-specific roles.

  11. 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

  12. Sepsis leads to thyroid impairment and dysfunction in rat model.

    PubMed

    Lin, Xingsheng; Shi, Songjing; Shi, Songchang

    2016-10-01

    Sepsis was a systemic response to a local infection. Apoptosis was observed in the experimental sepsis. In this study, cecal ligation and puncture (CLP)-induced sepsis was established in rats. We found that sepsis decreased thyroid hormone levels, including triiodothyronine (T3), thyroxine (T4), free T3 (fT3), and free T4 (fT4). Besides, we detected the increasing expression level of Caspase-3 and increasing ratio of TUNEL positive cells in the thyroid after sepsis. Furthermore, a series of pathological ultrastructural changes were observed in thyroid follicular epithelial cells by CLP-induced sepsis. This study established a sepsis animal model and provided the cellular and molecular basis for decoding the pathological mechanism in thyroid with the occurrence of sepsis.

  13. Sepsis Induces Telomere Shortening: a Potential Mechanism Responsible for Delayed Pathophysiological Events in Sepsis Survivors?

    PubMed Central

    Oliveira, Naara Mendes; Rios, Ester CS; de Lima, Thais Martins; Victorino, Vanessa Jacob; Barbeiro, Hermes; da Silva, Fabiano Pinheiro; Szabo, Csaba; Soriano, Francisco Garcia

    2016-01-01

    Sepsis survivors suffer from additional morbidities, including higher risk of readmissions, nervous system disturbances and cognitive dysfunction, and increased mortality, even several years after the initial episode of sepsis. In many ways, the phenotype of sepsis survivors resembles the phenotype associated with accelerated aging. Since telomere shortening is a hallmark of aging, we investigated whether sepsis also leads to telomere shortening. Male balb/c mice were divided into two groups: the control group received 100 μl of normal saline intraperitoneally (i.p.) and the sepsis group received 15 mg/kg of bacterial lipopolysaccharide i.p. After 48 h, animals were euthanized to collect blood, spleen and kidney. The human component of our study utilized blood samples obtained from patients in the trauma department and samples collected 7 d later in those patients who developed sepsis. Telomere length was measured by quantitative polymerase chain reaction. Since oxidative stress is a known inducer of telomere shortening, thiobarbituric acid–reactive substances and superoxide dismutase activity were analyzed to evaluate oxidative stress burden. Induction of endotoxemia in mice resulted in significant telomere shortening in spleen and kidney. Blood cells from patients who progressed to sepsis also exhibited a statistically significant reduction of telomere length. Endotoxemia in mice also induced an early-onset increase in oxidative stress markers but was not associated with a downregulation of telomerase protein expression. We conclude that endotoxemia and sepsis induce telomere shortening in various tissues and hypothesize that this may contribute to the pathogenesis of the delayed pathophysiological events in sepsis survivors. PMID:27925632

  14. Neonatal sepsis caused by Shewanella algae: A case report.

    PubMed

    Charles, Marie Victor Pravin; Srirangaraj, Sreenivasan; Kali, Arunava

    2015-01-01

    Sepsis remains a leading cause of mortality among neonates, especially in developing countries. Most cases of neonatal sepsis are attributed to Escherichia coli and other members of the Enterobacteriaceae family. Shewanella algae (S. algae) is a gram-negative saprophytic bacillus, commonly associated with the marine environment, which has been isolated from humans. Early onset neonatal sepsis caused by S. algae is uncommon. We report a case of S. algae blood stream infection in a newborn with early onset neonatal sepsis.

  15. 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

  16. Nociceptin system as a target in sepsis?

    PubMed

    Thomas, Róisín; Stover, Cordula; Lambert, David G; Thompson, Jonathan P

    2014-10-01

    The nociceptin system comprises the nociceptin receptor (NOP) and the ligand nociceptin/orphanin FQ (N/OFQ) that binds to the receptor. The archetypal role of the system is in pain processing but the NOP receptor is also expressed on immune cells. Activation of the NOP receptor is known to modulate inflammatory responses, such as mast-cell degranulation, neutrophil rolling, vasodilation, increased vascular permeability, adhesion molecule regulation and leucocyte recruitment. As there is a loss of regulation of inflammatory responses during sepsis, the nociceptin system could be a target for therapies aimed at modulating sepsis. This review details the known effects of NOP activation on leucocytes and the vascular endothelium and discusses the most recent human and animal data on the role of the nociceptin system in sepsis.

  17. Oxidative stress and mitochondrial dysfunction in sepsis.

    PubMed

    Galley, H F

    2011-07-01

    Sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit (ICU), despite advances in healthcare and science. Marked oxidative stress as a result of the inflammatory responses inherent with sepsis initiates changes in mitochondrial function which may result in organ damage. Normally, a complex system of interacting antioxidant defences is able to combat oxidative stress and prevents damage to mitochondria. Despite the accepted role that oxidative stress-mediated injury plays in the development of organ failure, there is still little conclusive evidence of any beneficial effect of systemic antioxidant supplementation in patients with sepsis and organ dysfunction. It has been suggested, however, that antioxidant therapy delivered specifically to mitochondria may be useful.

  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. The Use of Fluids in Sepsis

    PubMed Central

    Avila, Audrey A; 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

  20. Empyema following intra-abdominal sepsis.

    PubMed

    Ballantyne, K C; Sethia, B; Reece, I J; Davidson, K G

    1984-09-01

    Over the past 9 years, ten patients have presented to the Thoracic Unit, Glasgow Royal Infirmary, with 12 empyemas secondary to intra-abdominal sepsis. In eight patients, the presenting signs and symptoms were wrongly attributed to primary intra-thoracic pathology. All were subsequently found to have intra-abdominal sepsis. The presence of empyema after recent abdominal surgery or abdominal pain strongly suggests a diagnosis of ipsilateral subphrenic abscess. Adequate surgical drainage is essential. In our experience, limited thoracotomy with subdiaphragmatic extension offers the best access to both pleural and subphrenic spaces and provides the greatest chance of eradicating infection on both sides of the diaphragm.

  1. Sepsis and septic shock: a review.

    PubMed

    Chong, Josebelo; Dumont, Tiffany; Francis-Frank, Lyndave; Balaan, Marvin

    2015-01-01

    Sepsis and septic shock are a continuum of disease resulting from a complex host response to infection. They are major health issues in the United States, causing significant financial burden to the health care system in addition to multisystem morbidity and high rates of mortality. In recent decades, landmark trials in sepsis management have demonstrated improved mortality. Although the value of protocol-driven care is currently under question, it is clear that early recognition, prompt resuscitation, and timely use of antibiotics are of utmost importance.

  2. 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

  3. Sepsis Resuscitation in Resource-Limited Settings.

    PubMed

    Meier, Brian; Staton, Catherine

    2017-02-01

    Our evolving understanding of the physiologic processes that lead to sepsis has led to updated consensus guidelines outlining priorities in the recognition and treatment of septic patients. However, an enormous question remains when considering how to best implement these guidelines in settings with limited resources, which include rural US emergency departments and low- and middle-income countries. The core principles of sepsis management should be a priority in community emergency departments. Similarly, cost-effective interventions are key priorities in low- and middle-income countries; however, consideration must be given to the unique challenges associated with such settings.

  4. Incidence and mortality of sepsis, severe sepsis, and septic shock in intensive care unit patients with candidemia.

    PubMed

    Ng, Kevin; Schorr, Christa; Reboli, Annette C; Zanotti, Sergio; Tsigrelis, Constantine

    2015-08-01

    In this incidence study, of 16 074 patients admitted to the intensive care unit (ICU) from 1/1/2003 to 7/31/2011, 161 cases of candidemia were identified. The incidence of sepsis (27%), severe sepsis (31%), and septic shock (40%) was remarkably high in these cases of candidemia, as was the all-cause in-hospital mortality for sepsis (30%), severe sepsis (44%), and septic shock (65%).

  5. Limb salvage surgery

    PubMed Central

    Kadam, Dinesh

    2013-01-01

    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

  6. [Limb edema and lymphoscintigraphy].

    PubMed

    Bourgeois, P; Munck, D; Belgrado, J P; Leduc, O; Leduc, A

    2003-02-01

    Lymphoscintigraphic investigations represent techniques of nuclear medicine very contributive for the management and treatment of the limb edemas, either primary or secundary. Their principle is presented and methodologies proposed in the literature are reviewed. Their diagnostic contributions are detailed. The sensitivities and specificities of several protocols of investigation are reported. Some limitations of these examinations are analyzed and discussed. Clinical indications for their use are proposed and their interest with regard to the various treatments that can be applied to these limb edemas is discussed.

  7. JKTLD: Limb darkening coefficients

    NASA Astrophysics Data System (ADS)

    Southworth, John

    2015-11-01

    JKTLD outputs theoretically-calculated limb darkening (LD) strengths for equations (LD laws) which predict the amount of LD as a function of the part of the star being observed. The coefficients of these laws are obtained by bilinear interpolation (in effective temperature and surface gravity) in published tables of coefficients calculated from stellar model atmospheres by several researchers. Many observations of stars require the strength of limb darkening (LD) to be estimated, which can be done using theoretical models of stellar atmospheres; JKTLD can help in these circumstances.

  8. Elucidating the role of genomics in neonatal sepsis.

    PubMed

    Srinivasan, Lakshmi; Kirpalani, Haresh; Cotten, Charles Michael

    2015-12-01

    Sepsis is a major cause of neonatal morbidity and mortality, especially in vulnerable preterm populations. Immature immune defenses, and environmental and maternal factors contribute to this risk, with as many as a third of very preterm infants experiencing sepsis during their stay in the neonatal intensive care unit (NICU). Epidemiologic and twin studies have suggested that there is a genetic contribution to sepsis predilection. Several investigators have conducted candidate gene association studies on variants of specific interest and potential functional significance in neonatal sepsis. In this review, we describe details of studies that have evaluated genetic susceptibility in neonatal sepsis, and summarize findings from a review of candidate gene association studies.

  9. 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

  10. Neonatal sepsis: progress towards improved outcomes.

    PubMed

    Shane, Andi L; Stoll, Barbara J

    2014-01-01

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

  11. [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.

  12. [Pharmaconutrition with parenteral selenium in sepsis].

    PubMed

    Langlois, P L; de Oliveira Figliolino, L F; Hardy, G; Manzanares, W

    2014-04-01

    Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome.

  13. Pathogenesis of Multiple Organ Failure in Sepsis.

    PubMed

    Rossaint, Jan; Zarbock, Alexander

    2015-01-01

    Sepsis is a severe critical illness syndrome that arises from infectious insults. While the host immune system is generally beneficial, an overshooting and unregulated immune response can cause serious organ tissue injury. During sepsis, systemic hypotension, disturbed perfusion of the microcirculation, and direct tissue-toxicity caused by inflammatory immune reaction can occur and contribute to organ failure. The failure of two or more vital organ systems is termed multi-organ dysfunction syndrome (MODS) and resembles a very critical condition associated with high morbidity and mortality. Importantly, no specific treatment strategy exists to efficiently prevent the development of MODS during sepsis. In this review, we aim to identify the relevant molecular immunological pathways involved in the pathogenesis of MODS during sepsis. We believe that a detailed understanding of this mechanism is necessary for the development of new treatment approaches for septic patients. In particular, knowledge of the endogenous regulators keeping the balance between necessary immune system activation to combat infections and prevention of host tissue damage would greatly improve the chances for the development of effective interventions.

  14. Translational research and biomarkers in neonatal sepsis.

    PubMed

    Delanghe, Joris R; Speeckaert, Marijn M

    2015-12-07

    As neonatal sepsis is a severe condition, there is a call for reliable biomarkers to differentiate between infected and noninfected newborns. Although blood culture has been considered as the gold standard, this analysis is still too slow and limited by false negative results. Use of CRP is hampered by a physiological 3-day increase, resulting in a low sensitivity to detect sepsis at an early stage. A moderate diagnostic accuracy of other acute phase proteins has been demonstrated (serum amyloid A, procalcitonin, lipopolysaccharide binding protein, mannose binding lectin and hepcidin). In neonatal sepsis, changed chemokine/cytokine levels are observed before those of acute phase reactants. High IL-6, IL-8, IL-10 and TNF-α concentrations are detected in infected infants. Soluble interleukin-2 receptor has been used to identify bacteremia, whereas low plasma RANTES concentrations are characteristic for septicemia. Several cell adhesion molecules contribute to the pathogenesis of sepsis. As an upregulated CD64 expression on granulocytes is found within 1-6h after bacterial invasion, serial CD64 measurements could guide antibiotic therapy. An increased CD11b/CD18 density can improve the diagnosis, and a positive correlation between CD11b and the severity of systemic inflammation has been reported. An early increase in sCD14-ST presepsin is also observed during sepsis, whereas high sTREM-1 values in early-onset neonatal sepsis (EOS) have been associated with mortality. Biomarkers resulting from proteomics are also promising. A 4-biomarker 'mass restricted' score has been validated as diagnostic for intra-amniotic infection and/or inflammation. S100A8 in amniotic fluid is a strong predictor of an increased incidence of EOS. Proteomic analysis of cord blood has revealed altered protein expression patterns. The ApoSAA score is useful for identifying sepsis and could guide prescription of antibiotics. (1)H-NMR and GC-MS metabolomics allow to diagnose septic shock, which is

  15. Regulation of Cellular Immune Responses in Sepsis by Histone Modifications.

    PubMed

    Carson, W F; Kunkel, S L

    2017-01-01

    Severe sepsis, septic shock, and related inflammatory syndromes are driven by the aberrant expression of proinflammatory mediators by immune cells. During the acute phase of sepsis, overexpression of chemokines and cytokines drives physiological stress leading to organ failure and mortality. Following recovery from sepsis, the immune system exhibits profound immunosuppression, evidenced by an inability to produce the same proinflammatory mediators that are required for normal responses to infectious microorganisms. Gene expression in inflammatory responses is influenced by the transcriptional accessibility of the chromatin, with histone posttranslational modifications determining whether inflammatory gene loci are set to transcriptionally active, repressed, or poised states. Experimental evidence indicates that histone modifications play a central role in governing the cytokine storm of severe sepsis, and that aberrant chromatin modifications induced during the acute phase of sepsis may mediate chronic immunosuppression in sepsis survivors. This review will focus on the role of histone modifications in governing immune responses in severe sepsis, with an emphasis on specific leukocyte subsets and the histone modifications observed in these cells during chronic stages of sepsis. Additionally, the expression and function of chromatin-modifying enzymes (CMEs) will be discussed in the context of severe sepsis, as potential mediators of epigenetic regulation of gene expression in sepsis responses. In summary, this review will argue for the use of chromatin modifications and CME expression in leukocytes as potential biomarkers of immunosuppression in patients with severe sepsis.

  16. 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

    2016-06-17

    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.

  17. Redox therapy in neonatal sepsis: reasons, targets, strategy, and agents.

    PubMed

    Bajčetić, Milica; Spasić, Snežana; Spasojević, Ivan

    2014-09-01

    Neonatal sepsis is one of the most fulminating conditions in neonatal intensive care units. Antipathogen and supportive care are administered routinely, but do not deliver satisfactory results. In addition, the efforts to treat neonatal sepsis with anti-inflammatory agents have generally shown to be futile. The accumulating data imply that intracellular redox changes intertwined into neonatal sepsis redox cycle represent the main cause of dysfunction of mitochondria and cells in neonatal sepsis. Our aim here is to support the new philosophy in neonatal sepsis treatment, which involves the integration of mechanisms that are responsible for cellular dysfunction and organ failure, the recognition of the most important targets, and the selection of safe agents that can stop the neonatal sepsis redox cycle by hitting the hot spots. Redox-active agents that could be beneficial for neonatal sepsis treatment according to these criteria include lactoferrin, interleukin 10, zinc and selenium supplements, ibuprofen, edaravone, and pentoxifylline.

  18. Recognizing and managing severe sepsis: a common and deadly threat.

    PubMed

    Schlichting, Douglas; McCollam, Jill Shwed

    2007-06-01

    Through a literature review, the epidemiology and pathophysiology, including alterations in inflammation, coagulation, and impaired fibrinolysis that occur in the course of severe sepsis, is presented. Treatment guidelines that are evidence-based and endorsed by 11 professional societies representing multispecialty groups are described. Severe sepsis is common; 750,000 cases are estimated to occur annually in the United States. The mortality rate for severe sepsis still ranges from 30 to 50%, and is as high as 80 to 90% for septic shock and multiple organ dysfunction. Severe sepsis exists along a continuum initiated by a localized infection that triggers a systemic response. A cascade of inflammation and activation of the coagulation system associated with impaired fibrinolysis leads to alterations in microvascular circulation associated with organ dysfunction, severe sepsis, multiple organ dysfunction syndrome, and death. In an attempt to improve care and reduce mortality, the Surviving Sepsis Campaign and The Institute for Healthcare Improvement (IHI) have created two sepsis treatment bundles.

  19. Identifying Patients With Sepsis on the Hospital Wards.

    PubMed

    Bhattacharjee, Poushali; Edelson, Dana P; Churpek, Matthew M

    2017-04-01

    Sepsis contributes to up to half of all deaths in hospitalized patients, and early interventions, such as appropriate antibiotics, have been shown to improve outcomes. Most research has focused on early identification and treatment of patients with sepsis in the ED and the ICU; however, many patients acquire sepsis on the general wards. The goal of this review is to discuss recent advances in the detection of sepsis in patients on the hospital wards. We discuss data highlighting the benefits and limitations of the systemic inflammatory response syndrome (SIRS) criteria for screening patients with sepsis, such as its low specificity, as well as newly described scoring systems, including the proposed role of the quick sepsis-related organ failure assessment (qSOFA) score. Challenges specific to detecting sepsis on the wards are discussed, and future directions that use big data approaches and automated alert systems are highlighted.

  20. Mechanisms, detection, and potential management of microcirculatory disturbances in sepsis.

    PubMed

    Mohammed, Imran; Nonas, Stephanie A

    2010-04-01

    Despite improvements in resuscitation and treatment of sepsis, the morbidity and mortality remain unacceptably high. Microvascular dysfunction has been shown to play a significant role in the pathogenesis of sepsis and is a potential new target in the management of sepsis. Clinical studies, aided by new techniques that allow for real-time assessment of the microcirculation, have shown that disturbances in microcirculatory flow are common in sepsis and correlate with worse outcomes. Bedside measurement of microcirculatory perfusion has become simpler and more accessible, and may provide key insights into prognosis in sepsis and guide future therapeutics, much like mean arterial pressure (MAP), lactate, and mixed central oxygen saturation (SvO(2)) do now. The authors review here the role of microcirculatory dysfunction in sepsis and its potential role as a therapeutic target in sepsis.

  1. 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

  2. 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.

  3. Plasma soluble Tim-3 emerges as an inhibitor in sepsis: sepsis contrary to membrane Tim-3 on monocytes.

    PubMed

    Ren, F; Li, J; Jiang, X; Xiao, K; Zhang, D; Zhao, Z; Ai, J; Hou, C; Jia, Y; Han, G; Xie, L

    2015-11-01

    Immune dysfunction is the main characteristic of sepsis. T cell Ig and mucin domain protein 3 (Tim-3) on the monocytes has been reported to promote immune homeostasis during sepsis, but the influences of plasm soluble Tim-3 (sTim-3) on the immune system during sepsis remain unknown. Here, 100 patients with different severities of sepsis (40 sepsis, 42 severe sepsis, and 18 septic shock) were enrolled in this study. The Tim-3 and human leukocyte antigen-DR (HLA-DR) on the circulating monocytes were detected using flow cytometry. Plasma sTim-3 was detected by enzyme-linked immunosorbent assay. Inflammatory factors and two kinds of A disintegrin and metalloprotease (ADAM) - ADAM10 and ADAM17 were assessed. The Tim-3 and HLA-DR on the monocytes decreased with increasing sepsis severity. The sTim-3 was reduced in the sepsis and severe sepsis patients but was elevated in the septic shock patients who exhibited significant immunosuppression as predicted by HLA-DR. sTim-3 levels were negatively correlated with IL-12 and TNF-α. ADAM10 and ADAM17, sheddases of Tim-3, exhibited trends toward elevations in the septic shock group. In conclusion, sTim-3 was involved in the development of sepsis. The homeostasis-promoting role of the Tim-3 on the monocytes was disrupted, while the inhibitory role of sTim-3 emerged during sepsis-induced immunosuppression.

  4. 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.

  5. Lengthening of replanted or revascularized lower limbs: is length discrepancy a contraindication for limb salvage?

    PubMed

    Parmaksizoglu, Fatih; Beyzadeoglu, Tahsin

    2002-08-01

    Some replantation cases require substantial bone shortening for primary closure. Leg-length discrepancy can be restored by lengthening of the replanted or revascularized extremities. Between 1991 and 2000, four patients with four total and two subtotal below-knee amputations had replantation or revascularization for their severely damaged extremities. All of them had extensive debridement, vascular repair, bone shortening and nerve repair for sensibility of their soles. One of the replanted extremities failed and had to undergo below-knee amputation because of sepsis. No other infection or vascular complications were encountered following the replantations or revascularizations. After bony consolidation, four legs were lengthened; for elimination of length discrepancy in three cases, and for obtaining balanced body proportion in one case in which the other leg was also amputated. In all procedures, a unilateral dynamic axial external fixator was used. The lengthening was performed from the proximal tibial metaphysis, with a subperiosteal osteotomy. Evaluation of injury according to the Mangled Extremity Severity Score (MESS) would encourage the surgeon to avoid salvage surgery with a shortened extremity, because of the required debridement of soft tissue and bone. These authors think the amount of limb shortening is not a major criterion in evaluating a traumatic total or subtotal below-knee amputation for salvage replantation or revascularization. A knee that has stable joint motion and the possibility of preservation of sensibility of the sole broadens the scope of indications for limb salvage, even with deliberate shortening that can be restored by lengthening; length discrepancy is not a contraindication for limb salvage.

  6. The effect of HIV infection on the incidence and severity of circular external fixator pin track sepsis: a retrospective comparative study of 229 patients.

    PubMed

    Ferreira, Nando; Marais, Leonard Charles

    2014-08-01

    Pin track sepsis is a common complication of circular external fixation. HIV status has been implicated as an independent risk factor for the development of pin track infection and has been cited as a reason not to attempt complex limb reconstruction in HIV-positive patients. This retrospective review of patients treated with circular external fixators looked at the incidence of pin track sepsis in HIV-positive, HIV-negative and patients whose HIV status was unknown. The records of 229 patients, 40 of whom were HIV-positive, were reviewed. The overall incidence of pin track sepsis was 22.7 %. HIV infection did not affect the incidence of pin track sepsis (p = 0.9). The severity of pin track sepsis was not influenced by HIV status (p = 0.9) or CD4 count (p = 0.2). With the employment of meticulous pin insertion techniques and an effective postoperative pin track care protocol, circular external fixation can be used safely in HIV-positive individuals.

  7. 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.

  8. The Glyoxalase System and Methylglyoxal-Derived Carbonyl Stress in Sepsis: Glycotoxic Aspects of Sepsis Pathophysiology

    PubMed Central

    Schmoch, Thomas; Uhle, Florian; Siegler, Benedikt H.; Fleming, Thomas; Morgenstern, Jakob; Nawroth, Peter P.; Weigand, Markus A.; Brenner, Thorsten

    2017-01-01

    Sepsis remains one of the leading causes of death in intensive care units. Although sepsis is caused by a viral, fungal or bacterial infection, it is the dysregulated generalized host response that ultimately leads to severe dysfunction of multiple organs and death. The concomitant profound metabolic changes are characterized by hyperglycemia, insulin resistance, and profound transformations of the intracellular energy supply in both peripheral and immune cells. A further hallmark of the early phases of sepsis is a massive formation of reactive oxygen (ROS; e.g., superoxide) as well as nitrogen (RNS; e.g., nitric oxide) species. Reactive carbonyl species (RCS) form a third crucial group of highly reactive metabolites, which until today have been not the focus of interest in sepsis. However, we previously showed in a prospective observational clinical trial that patients suffering from septic shock are characterized by significant methylglyoxal (MG)-derived carbonyl stress, with the glyoxalase system being downregulated in peripheral blood mononuclear cells. In this review, we give a detailed insight into the current state of research regarding the metabolic changes that entail an increased MG-production in septicemia. Thus, we point out the special role of the glyoxalase system in the context of sepsis. PMID:28304355

  9. 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.

  10. Aeromonas hydrophila Sepsis Mimicking Vibrio vulnificus Infection.

    PubMed

    Park, Se Young; Nam, Hyun Min; Park, Kun; Park, Seok Don

    2011-09-01

    Aeromonas hydrophila is a facultatively anaerobic, asporogenous gram-negative rod that has often been regarded as an opportunistic pathogen in hosts with impairment of a local or general defense mechanism. A 68-year-old alcoholic woman presented with shock and gangrene on the right arm. At first, her clinical presentations were severe painful erythematous swelling that worsened within a few hours with development of gangrene, edema, and blisters. Bullous fluid and blood cultures yielded A. hydrophila. Histopathological findings of sections obtained from the vesicle revealed subepidermal vesicles; necrosis of the epidermis, papillary dermis, and subcutaneous fat; and massive hemorrhage in the subcutis. Despite all efforts to save the patient, she died 8 hours after admission. Clinical features of A. hydrophila sepsis resemble those of Vibrio vulnificus sepsis. Therefore, in addition to the case report, we compared the cultural, biochemical, and morphological differences between A. hydrophila and V. vulnificus for facilitation of early and accurate identification of the causative agent.

  11. Risk assessment in neonatal early onset sepsis.

    PubMed

    Mukhopadhyay, Sagori; Puopolo, Karen M

    2012-12-01

    The incidence of neonatal early onset sepsis has declined with the widespread use of intrapartum antibiotic therapies, yet early onset sepsis remains a potentially fatal condition, particularly among very low birth-weight infants. Clinical signs of neonatal infection are nonspecific and may be absent in the immediate postnatal period. Maternal and infant clinical characteristics, as well as infant laboratory values, have been used to identify newborns at risk and to administer empiric antibiotic therapy to prevent progression to more severe illness. Such approaches result in the evaluation of approximately 15% of asymptomatic term and late preterm infants and of nearly all preterm infants. The development of multivariate predictive models may provide more accurate methods of identifying newborns at highest risk and allow for more limited newborn antibiotic exposures.

  12. Carbon monoxide in the treatment of sepsis.

    PubMed

    Nakahira, Kiichi; Choi, Augustine M K

    2015-12-15

    Carbon monoxide (CO), a low-molecular-weight gas, is endogenously produced in the body as a product of heme degradation catalyzed by heme oxygenase (HO) enzymes. As the beneficial roles of HO system have been elucidated in vitro and in vivo, CO itself has also been reported as a potent cytoprotective molecule. Whereas CO represents a toxic inhalation hazard at high concentration, low-dose exogenous CO treatment (~250-500 parts per million) demonstrates protective functions including but not limited to the anti-inflammatory and antiapoptotic effects in preclinical models of human diseases. Of note, CO exposure confers protection in animal models of sepsis by inhibiting inflammatory responses and also enhancing bacterial phagocytosis in leukocytes. These unique functions of CO including both dampening inflammation and promoting host defense mechanism are mediated by multiple pathways such as autophagy induction or biosynthesis of specialized proresolving lipid mediators. We suggest that CO gas may represent a novel therapy for patients with sepsis.

  13. The Parenteral Vitamin C Improves Sepsis and Sepsis-Induced Multiple Organ Dysfunction Syndrome via Preventing Cellular Immunosuppression

    PubMed Central

    Chai, Yan-Fen

    2017-01-01

    Cellular immunosuppression appears to be involved in sepsis and sepsis-induced multiple organ dysfunction syndrome (MODS). Recent evidence showed that parenteral vitamin C (Vit C) had the ability to attenuate sepsis and sepsis-induced MODS. Herein, we investigated the impact of parenteral Vit C on cellular immunosuppression and the therapeutic value in sepsis. Using cecal ligation and puncture (CLP), sepsis was induced in WT and Gulo−/− mice followed with 200 mg/Kg parenteral Vit C administration. The immunologic functions of CD4+CD25+ regulatory T cells (Tregs) and CD4+CD25− T cells, as well as the organ functions, were determined. Administration of parenteral Vit C per se markedly improved the outcome of sepsis and sepsis-induced MODS of WT and Gulo−/− mice. The negative immunoregulation of Tregs was inhibited, mainly including inhibiting the expression of forkhead helix transcription factor- (Foxp-) 3, cytotoxic T lymphocyte associated antigen- (CTLA-) 4, membrane associated transforming growth factor-β (TGF-βm+), and the secretion of inhibitory cytokines [including TGF-β and interleukin- (IL-) 10], as well as CD4+ T cells-mediated cellular immunosuppression which was improved by parenteral Vit C in WT and Gulo−/− septic mice. These results suggested that parenteral Vit C has the ability to improve the outcome of sepsis and sepsis-induced MODS and is associated with improvement in cellular immunosuppression. PMID:28210072

  14. The Parenteral Vitamin C Improves Sepsis and Sepsis-Induced Multiple Organ Dysfunction Syndrome via Preventing Cellular Immunosuppression.

    PubMed

    Gao, Yu-Lei; Lu, Bin; Zhai, Jian-Hua; Liu, Yan-Cun; Qi, Hai-Xia; Yao, Ying; Chai, Yan-Fen; Shou, Song-Tao

    2017-01-01

    Cellular immunosuppression appears to be involved in sepsis and sepsis-induced multiple organ dysfunction syndrome (MODS). Recent evidence showed that parenteral vitamin C (Vit C) had the ability to attenuate sepsis and sepsis-induced MODS. Herein, we investigated the impact of parenteral Vit C on cellular immunosuppression and the therapeutic value in sepsis. Using cecal ligation and puncture (CLP), sepsis was induced in WT and Gulo(-/-) mice followed with 200 mg/Kg parenteral Vit C administration. The immunologic functions of CD4(+)CD25(+) regulatory T cells (Tregs) and CD4(+)CD25(-) T cells, as well as the organ functions, were determined. Administration of parenteral Vit C per se markedly improved the outcome of sepsis and sepsis-induced MODS of WT and Gulo(-/-) mice. The negative immunoregulation of Tregs was inhibited, mainly including inhibiting the expression of forkhead helix transcription factor- (Foxp-) 3, cytotoxic T lymphocyte associated antigen- (CTLA-) 4, membrane associated transforming growth factor-β (TGF-β(m+)), and the secretion of inhibitory cytokines [including TGF-β and interleukin- (IL-) 10], as well as CD4(+) T cells-mediated cellular immunosuppression which was improved by parenteral Vit C in WT and Gulo(-/-) septic mice. These results suggested that parenteral Vit C has the ability to improve the outcome of sepsis and sepsis-induced MODS and is associated with improvement in cellular immunosuppression.

  15. The protein C pathway and sepsis.

    PubMed

    Della Valle, Patrizia; Pavani, Giulia; D'Angelo, Armando

    2012-03-01

    After the discovery of the key components of the protein C (PC) pathway a beneficial effect on survival of the infusion of activated protein C (APC) in animal models of sepsis was demonstrated, leading to the development of recombinant human activated protein C (rh-APC) as a therapeutic agent. It soon became clear that rather than the anticoagulant and profibrinolytic activities of APC, its anti-inflammatory and cytoprotective properties played a major role in the treatment of patients with severe sepsis. Such properties affect the response to inflammation of endothelial cells and leukocytes and are exerted through binding of APC to at least five receptors with intracellular signaling. The main APC protective mechanism involves binding of the Gla-domain to the endothelial protein C receptor (EPCR) and cleavage of protease activated receptor 1 (PAR-1), eliciting suppression of proinflammatory cytokines synthesis and of intracellular proapoptotic pathways and activation of endothelial barrier properties. However, thrombin cleaves PAR-1 with much higher catalytic efficiency, followed by pro-inflammatory, pro-apoptotic and barrier disruptive intracellular signaling, and it is unclear how APC can exert a protective activity through the cleavage of PAR-1 when thrombin is also present in the same environment. Interestingly, in endothelial cell cultures, PAR-1 cleavage by thrombin results in anti-inflammatory and barrier protective signaling provided occupation of EPCR by the PC gla-domain, raising the possibility that the beneficial effects of rh-APC might be recapitulated in vivo by administration of h-PC zymogen to patients with severe sepsis. Recent reports of h-PC infusion in animal models of sepsis support this hypothesis.

  16. 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

  17. Coagulation in patients with severe sepsis.

    PubMed

    Levi, Marcel; Poll, Tom van der

    2015-02-01

    In the majority of patients with severe sepsis, systemic activation of coagulation is present. Increasing evidence points to an extensive cross-talk between coagulation and inflammation that may play an important role in the pathogenesis of sepsis. Inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Proinflammatory cytokines and other mediators are capable of activating the coagulation system and downregulating important physiological anticoagulant pathways. Activation of the coagulation system and ensuing thrombin generation is dependent on expression of tissue factor on activated mononuclear cells and endothelial cells, and is insufficiently counteracted by TFPI. Simultaneously, endothelial-bound anticoagulant mechanism, in particular the protein C system, is shutoff by proinflammatory cytokines. In addition, fibrin removal is severely inhibited, because of inactivation of the fibrinolytic system, caused by an upregulation of its main inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Increased fibrin formation and impaired removal lead to (micro)vascular thrombosis, which may result in tissue ischemia and subsequent organ damage. The cornerstone of the management of coagulation in sepsis is the specific and vigorous treatment of the underlying disorder. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and initial clinical studies. Heparin may be an effective anticoagulant approach and alternative strategies comprise restoration of physiological anticoagulant pathways.

  18. Ethyl pyruvate: a novel treatment for sepsis.

    PubMed

    Fink, Mitchell P

    2007-01-01

    Ethyl pyruvate (EP), a simple aliphatic ester derived from pyruvic acid, improves survival and ameliorates organ system dysfunction in mice with peritonitis induced by caecal ligation and perforation, even when treatment is started as late as 12-24 hours after the onset of sepsis. In studies using lipopolysaccharide-stimulated RAW 264.7 murine macrophage like cells, EP inhibits activation of the pro-inflammatory transcription factor, NF-kappaB, and down regulates secretion of a number of pro-inflammatory cytokines, such as tumour necrosis factor (TNF). In this reductionist in vitro system, EP also blocks secretion of the late-appearing pro inflammatory cytokine-like molecule, high mobility group box 1 (HMGB1). In murine models of endotoxaemia or sepsis, treatment with EP decreases circulating levels of TNF and HMGB1. While the molecular events responsible for the salutary effects of EP remain to be elucidated, one mechanism may involve covalent modification of a critical thiol residue in the p65 component of NF-kappaB. EP warrants evaluation as a therapeutic agent for the treatment of sepsis in humans.

  19. Particularities regarding the etiology of sepsis in forensic services.

    PubMed

    Dermengiu, Dan; Curca, George Cristian; Ceausu, Mihai; Hostiuc, Sorin

    2013-09-01

    If in clinical practice definitive diagnostic criteria had been established, after death sepsis is often difficult to diagnose, especially if a site of origin is not found or if no clinical data are available. This article will analyze the etiology of sepsis in a medical-legal service with emphasis on the differences in diagnosing it in clinical and forensic environments. A total of 78 cases of sepsis cases diagnosed or confirmed at the autopsy were selected. The etiological agent was determined either during the hospitalization or by postmortem bacteriology. A high prevalence of Gram-negative sepsis was found, especially multidrug-resistant micro-organisms. Most frequent etiological agents were Acinetobacter baumannii, Escherichia coli, Enterobacter, Enterococcus, Pseudomonas, and Klebsiella. Polymicrobial sepsis is much more frequent than in nonforensic cases. In legal medicine, the prevalence of Gram-negative sepsis is much higher than in nonforensic autopsies, and the point of origin is shifted toward the skin and the gastrointestinal system.

  20. Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

    PubMed Central

    Delano, Matthew J.; Ward, Peter A.

    2016-01-01

    Sepsis is a systemic inflammatory response induced by an infection, leading to organ dysfunction and mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the interplay between inflammatory and antiinflammatory responses. With advances in intensive care management and goal-directed interventions, early sepsis mortality has diminished, only to surge later after “recovery” from acute events, prompting a search for sepsis-induced alterations in immune function. Sepsis is well known to alter innate and adaptive immune responses for sustained periods after clinical “recovery,” with immunosuppression being a prominent example of such alterations. Recent studies have centered on immune-modulatory therapy. These efforts are focused on defining and reversing the persistent immune cell dysfunction that is associated with mortality long after the acute events of sepsis have resolved. PMID:26727230

  1. Incidence and Prognosis of Atrial Fibrillation in Patients With Sepsis

    PubMed Central

    Wells, Gretchen L.; Morris, Peter E.

    2011-01-01

    Background Although the mortality rate among patients with sepsis is declining, the incidence of both sepsis and sepsis-related deaths is increasing, likely due to its presence in a growing elderly population. As atrial fibrillation is more common in the elderly, we hypothesize that its presence will be associated with greater mortality among patients with sepsis. Methods The Medical Intensive Care Unit (MICU) database of a large tertiary care medical center was queried for sepsis-related codes and atrial fibrillation. Results Atrial fibrillation was associated with older age and a higher mortality in this series of patients with sepsis. Conclusions Whether atrial fibrillation is a marker of disease severity or contributes to mortality is uncertain. Further studies are necessary to determine optimal management.

  2. Apoptosis and caspases regulate death and inflammation in sepsis.

    PubMed

    Hotchkiss, Richard S; Nicholson, Donald W

    2006-11-01

    Although the prevailing concept has been that mortality in sepsis results from an unbridled hyper-inflammatory cytokine-mediated response, the failure of more than 30 clinical trials to treat sepsis by controlling this cytokine response requires a 'rethink' of the molecular mechanism underpinning the development of sepsis. As we discuss here, remarkable new studies indicate that most deaths from sepsis are actually the result of a substantially impaired immune response that is due to extensive death of immune effector cells. Rectification of this apoptotic-inflammatory imbalance using modulators of caspases and other components of the cell-death pathway have shown striking efficacy in stringent animal models of sepsis, indicating an entirely novel path forward for the clinical treatment of human sepsis.

  3. The pediatric sepsis biomarker risk model: potential implications for sepsis therapy and biology

    PubMed Central

    Alder, Matthew N; Lindsell, Christopher J; Wong, Hector R

    2015-01-01

    Sepsis remains a major cause of morbidity and mortality in adult and pediatric intensive care units. Heterogeneity of demographics, comorbidities, biological mechanisms, and severity of illness leads to difficulty in determining which patients are at highest risk of mortality. Determining mortality risk is important for weighing the potential benefits of more aggressive interventions and for deciding whom to enroll in clinical trials. Biomarkers can be used to parse patients into different risk categories and can outperform current methods of patient risk stratification based on physiologic parameters. Here we review the Pediatric Sepsis Biomarker Risk Model that has also been modified and applied to estimate mortality risk in adult patients. We compare the two models and speculate on the biological implications of the biomarkers in patients with sepsis. PMID:24754535

  4. Delayed amputation in lower limb trauma: an analysis of factors leading to delayed amputation.

    PubMed

    Thiagarajan, P

    1999-03-01

    An in-depth analysis of the course of events leading to 49 delayed amputation of the lower extremity in 47 patients with open lower limb fractures is presented. Seventeen amputations were performed within one month mainly for vascular reasons. Eleven were between one month and one year, due to persistent sepsis and 21 amputations were performed more than a year after the original injury for infected non-union. Below-knee amputation was done in 32 limbs, above-knee amputation in 13 limbs and Symes' amputation in 4 limbs. The delay in timing of the amputation was analysed with respect to the nature of the injury, the primary treatment and the Mangled Extremity Severity Score (MESS). The MESS score was computed for all injuries and a score of 7 or more predicted an early amputation. We suggest that in all severe lower limb injuries, particularly in Type III C fractures with associated neurological injury, the benefits of an early amputation be considered as an alternative to a limb salvage procedure.

  5. 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

  6. 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

  7. 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

  8. Mass spectrometry for the discovery of biomarkers of sepsis.

    PubMed

    Ludwig, Katelyn R; Hummon, Amanda B

    2017-03-28

    Sepsis is a serious medical condition that occurs in 30% of patients in intensive care units (ICUs). Early detection of sepsis is key to prevent its progression to severe sepsis and septic shock, which can cause organ failure and death. Diagnostic criteria for sepsis are nonspecific and hinder a timely diagnosis in patients. Therefore, there is currently a large effort to detect biomarkers that can aid physicians in the diagnosis and prognosis of sepsis. Mass spectrometry is often the method of choice to detect metabolomic and proteomic changes that occur during sepsis progression. These "omics" strategies allow for untargeted profiling of thousands of metabolites and proteins from human biological samples obtained from septic patients. Differential expression of or modifications to these metabolites and proteins can provide a more reliable source of diagnostic biomarkers for sepsis. Here, we focus on the current knowledge of biomarkers of sepsis and discuss the various mass spectrometric technologies used in their detection. We consider studies of the metabolome and proteome and summarize information regarding potential biomarkers in both general and neonatal sepsis.

  9. Haemophilus influenzae: a forgotten cause of neonatal sepsis?

    PubMed

    Dobbelaere, A; Jeannin, P; Bovyn, T; Ide, L

    2015-06-01

    Due to the introduction of the conjugate vaccine against serotype b, neonatal sepsis caused by Haemophilus influenzae became very rare. There is little data in Belgium concerning the prevalence of H. influenzae early onset neonatal sepsis and articles about neonatal sepsis and H. influenzae published in the last decade are scarce. We report two invasive infections with a non-typeable H. influenzae. These cases show that neonatal sepsis caused by non-typeable H. influenzae may be underestimated and we believe that there is need for a better registration of this kind of infection.

  10. Mitochondrial Dysfunction and Immune Cell Metabolism in Sepsis

    PubMed Central

    2017-01-01

    Sepsis is a life threatening condition mediated by systemic infection, but also triggered by hemorrhage and trauma. These are significant causes of organ injury implicated in morbidity and mortality, as well as post-sepsis complications associated with dysfunction of innate and adaptive immunity. The role of cellular bioenergetics and loss of metabolic plasticity of immune cells is increasingly emerging in the pathogenesis of sepsis. This review describes mitochondrial biology and metabolic alterations of immune cells due to sepsis, as well as indicates plausible therapeutic opportunities. PMID:28378540

  11. Incidence of Post-Operative Sepsis and Role of Charlson Co-Morbidity Score for Predicting Postoperative Sepsis.

    PubMed

    Emami-Razavi, Seyed Hassan; Mohammadi, Atefeh; Alibakhshi, Abbas; Jalali, Mehdi; Ghajarzadeh, Mahsa

    2016-05-01

    Sepsis and septic shock are among mortality causes following major surgeries. The Charlson co-morbidity index consists of 19 weighted categories related to chronic health which measures the burden of co-morbidity. The goal of this study was to determine the incidence of postoperative sepsis in patients underwent gynecological and gastrointestinal cancer surgeries and predictive role of Charlson index for this situation. Two hundred and twenty-two patients who underwent gynecological and gastrointestinal cancer surgeries were evaluated. Sixty-four (28.6%) patients developed SIRS postoperatively. Forty-four (19.7%) patients developed sepsis postoperatively. Mean age, duration of hospitalization and surgery, the Charlson score were significantly higher in patients who developed sepsis than other cases. Blood transfusion and Charlson score were independent predictors of sepsis occurrence. Charlson co-morbidity index is a predictive factor for developing postoperative sepsis.

  12. 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

  13. Limb salvage using advanced technologies: a case report.

    PubMed

    Frykberg, Robert G; O'Connor, Rachel M; Tallis, Arthur; Tierney, Edward

    2015-02-01

    Patients with severe acute and chronic lower extremity wounds often present a significant challenge in terms of limb salvage. In addition to control of infection, assuring adequate perfusion and providing standard wound care, advanced modalities are often required to facilitate final wound closure. We herein present a case study on a diabetic patient with gangrene and necrotising soft-tissue infection who underwent a forefoot pedal amputation to control the sepsis. Despite his non invasive vascular studies demonstrating poor healing potential at this level, he was not deemed suitable for revascularisation by our vascular surgeons and ankle-level amputation was recommended. Nonetheless, over a 5-month period using multiple advanced wound care therapies, wound closure was ultimately achieved.

  14. 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.

  15. Vitamin D Deficiency in Human and Murine Sepsis*

    PubMed Central

    Parekh, Dhruv; Patel, Jaimin M.; Scott, Aaron; Lax, Sian; Dancer, Rachel C. A.; D’Souza, Vijay; Greenwood, Hannah; Fraser, William D.; Gao, Fang; Sapey, Elizabeth; Perkins, Gavin D.

    2017-01-01

    Objectives: Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and ICU mortality but causality of these associations has not been demonstrated. To determine whether sepsis and severe sepsis are associated with vitamin D deficiency and to determine whether vitamin D deficiency influences the severity of sepsis. Design, Setting, and Patients: Sixty-one patients with sepsis and severe sepsis from two large U.K. hospitals and 20 healthy controls were recruited. Murine models of cecal ligation and puncture and intratracheal lipopolysaccharide were undertaken in normal and vitamin D deficient mice to address the issue of causality. Measurements and Main Results: Patients with severe sepsis had significantly lower concentrations of 25-hydroxyvitamin D3 than patients with either mild sepsis or age-matched healthy controls (15.7 vs 49.5 vs 66.5 nmol/L; p = 0.0001). 25-hydroxyvitamin D3 concentrations were significantly lower in patients who had positive microbiologic culture than those who were culture negative (p = 0.0023) as well as those who died within 30 days of hospital admission (p = 0.025). Vitamin D deficiency in murine sepsis was associated with increased peritoneal (p = 0.037), systemic (p = 0.019), and bronchoalveolar lavage (p = 0.011) quantitative bacterial culture. This was associated with reduced local expression of the cathelicidin-related antimicrobial peptide as well as evidence of defective macrophage phagocytosis (p = 0.029). In the intratracheal lipopolysaccharide model, 1,500 IU of intraperitoneal cholecalciferol treatment 6 hours postinjury reduced alveolar inflammation, cellular damage, and hypoxia. Conclusions: Vitamin D deficiency is common in severe sepsis. This appears to contribute to the development of the condition in clinically relevant murine models and approaches to correct vitamin D deficiency in patients with sepsis should be developed. PMID:27632669

  16. Vasospastic Limb Ischemia Presenting Acute and Chronic Limb Ischemia

    PubMed Central

    2014-01-01

    Vasospastic limb ischemia might have been underappreciated compared to vasospasm in other territories such as heart and brain. However, an increasing awareness of this vascular disorder can be translated to an improved patients’ care. Herein, we report a case of vasospasm presenting acute and chronic limb ischemia in four extremities. PMID:24995065

  17. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1989-08-15

    The subject of this report is progress during the quarter for Phase I -- Design and Permitting, Phase II -- Coolside/LIMB Construction, Start-Up and Phase III -- Operation, Data Collection, Reporting and Disposition. Under Phase I, Task 2, Consol Technology Transfer, Consol R D continued to review the status of the Coolside installation and identified construction details which required additional action. Activities in Task 4.0 -- Permitting and Licensing have focused on finalizing a subcontract agreement for trucking the DOE Coolside/LIMB ash to a solid waste landfill. Under Phase II, Task 1, Project Management, purchase orders were placed with two (2) lime suppliers for supplying the specified hydrated lime to be used for the Coolside test program. For Subtask 2.2 -- Sorbent Feed System Installation, the construction and installation of the sorbent feed system has been completed. Under Phase III, Subtask 2.1, Optimization of the Coolside sorbent feed system, the ash recycle system and the caustic injection system were initiated. 3 figs.

  18. LDTK: Limb Darkening Toolkit

    NASA Astrophysics Data System (ADS)

    Parviainen, H.; Aigrain, S.

    2015-11-01

    We present a PYTHON package LDTK that automates the calculation of custom stellar limb-darkening (LD) profiles and model-specific limb-darkening coefficients using the library of PHOENIX-generated specific intensity spectra by Husser et al. The aim of the package is to facilitate analyses requiring custom generated LD profiles, such as the studies of exoplanet transits - especially transmission spectroscopy, where the transit modelling is carried out for custom narrow passbands - eclipsing binaries, interferometry, and microlensing events. First, LDTK can be used to compute custom LD profiles with uncertainties propagated from the uncertainties in the stellar parameter estimates. Secondly, LDTK can be used to estimate the LD-model-specific coefficients with uncertainties for the most common LD models. Thirdly, LDTK can be directly integrated into the log posterior computation of any pre-existing modelling code with minimal modifications. The last approach can be used to constrain the LD model parameter space directly by the LD profile, allowing for the marginalization over the LD parameter space without the need to approximate the constraint from the LD profile using a prior.

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

    PubMed Central

    McLymont, Natalie

    2016-01-01

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

  20. The Endothelial Glycocalyx: New Diagnostic and Therapeutic Approaches in Sepsis

    PubMed Central

    Koczera, Patrick

    2016-01-01

    Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The endothelial glycocalyx is one of the earliest sites involved during sepsis. This fragile layer is a complex network of cell-bound proteoglycans, glycosaminoglycan side chains, and sialoproteins lining the luminal side of endothelial cells with a thickness of about 1 to 3 μm. Sepsis-associated alterations of its structure affect endothelial permeability and result in the liberation of endogenous damage-associated molecular patterns (DAMPs). Once liberated in the circulatory system, DAMPs trigger the devastating consequences of the proinflammatory cascades in sepsis and septic shock. In this way, the injury to the glycocalyx with the consecutive release of DAMPs contributes to a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and septic cardiomyopathy. Moreover, the extent of glycocalyx degradation serves as a marker of endothelial dysfunction and sepsis severity. In this review, we highlight the crucial role of the glycocalyx in sepsis as a diagnostic tool and discuss the potential of members of the endothelial glycocalyx serving as hopeful therapeutic targets in sepsis-associated multiple organ failures. PMID:27699168

  1. B cells enhance early innate immune responses during bacterial sepsis

    PubMed Central

    Kelly-Scumpia, Kindra M.; Scumpia, Philip O.; Weinstein, Jason S.; Delano, Matthew J.; Cuenca, Alex G.; Nacionales, Dina C.; Wynn, James L.; Lee, Pui Y.; Kumagai, Yutaro; Efron, Philip A.; Akira, Shizuo; Wasserfall, Clive; Atkinson, Mark A.

    2011-01-01

    Microbes activate pattern recognition receptors to initiate adaptive immunity. T cells affect early innate inflammatory responses to viral infection, but both activation and suppression have been demonstrated. We identify a novel role for B cells in the early innate immune response during bacterial sepsis. We demonstrate that Rag1−/− mice display deficient early inflammatory responses and reduced survival during sepsis. Interestingly, B cell–deficient or anti-CD20 B cell–depleted mice, but not α/β T cell–deficient mice, display decreased inflammatory cytokine and chemokine production and reduced survival after sepsis. Both treatment of B cell–deficient mice with serum from wild-type (WT) mice and repletion of Rag1−/− mice with B cells improves sepsis survival, suggesting antibody-independent and antibody-dependent roles for B cells in the outcome to sepsis. During sepsis, marginal zone and follicular B cells are activated through type I interferon (IFN-I) receptor (IFN-α/β receptor [IFNAR]), and repleting Rag1−/− mice with WT, but not IFNAR−/−, B cells improves IFN-I–dependent and –independent early cytokine responses. Repleting B cell–deficient mice with the IFN-I–dependent chemokine, CXCL10 was also sufficient to improve sepsis survival. This study identifies a novel role for IFN-I–activated B cells in protective early innate immune responses during bacterial sepsis. PMID:21746813

  2. New perspectives on immunomodulatory therapy for bacteraemia and sepsis.

    PubMed

    Opal, Steven M

    2010-12-01

    Systemic immune dysregulation is generally acknowledged to be the fundamental molecular mechanism that underlies the pathophysiology of severe sepsis and septic shock. In the presence of a systemic infection, microbial pathogens and their soluble mediators induce generalised immune activation and coagulation activation, leading to severe sepsis and septic shock. For decades, immune-based therapies have been devised with the specific intent of inhibiting the pro-inflammatory events that are thought to precipitate the septic process. Despite a clear therapeutic rationale based upon the available experimental evidence, anti-inflammatory therapies targeting the innate or acquired immune response have largely been unsuccessful in clinical trials of sepsis. Compelling evidence now exists that a prolonged state of sepsis-induced immune suppression follows the initial period of stabilisation and resuscitation in many critically ill patients. Sepsis-related immune suppression is evidenced by histological findings of markedly enhanced lymphocytic and monocytic apoptosis, poor response to neoantigens and recall antigens, and increased incidence of infections by opportunistic pathogens. Candidiasis, cytomegalovirus activation and secondary infections by relatively avirulent bacterial pathogens such as Stenotrophomonas and Acinetobacter spp. are commonplace in septic patients during prolonged Intensive Care Unit stays. Immunological tools to detect sepsis-induced immunosuppression are now available, and novel immunoadjuvants are in development to re-establish immune competence in sepsis patients. The intelligent use of immunomodulatory agents in sepsis will necessitate a personalised medicine approach to treat each patient at the appropriate time and with the optimal therapy.

  3. Fluid resuscitation in human sepsis: Time to rewrite history?

    PubMed

    Byrne, Liam; Van Haren, Frank

    2017-12-01

    Fluid resuscitation continues to be recommended as the first-line resuscitative therapy for all patients with severe sepsis and septic shock. The current acceptance of the therapy is based in part on long history and familiarity with its use in the resuscitation of other forms of shock, as well as on an incomplete and incorrect understanding of the pathophysiology of sepsis. Recently, the safety of intravenous fluids in patients with sepsis has been called into question with both prospective and observational data suggesting improved outcomes with less fluid or no fluid. The current evidence for the continued use of fluid resuscitation for sepsis remains contentious with no prospective evidence demonstrating benefit to fluid resuscitation as a therapy in isolation. This article reviews the historical and physiological rationale for the introduction of fluid resuscitation as treatment for sepsis and highlights a number of significant concerns based on current experimental and clinical evidence. The research agenda should focus on the development of hyperdynamic animal sepsis models which more closely mimic human sepsis and on experimental and clinical studies designed to evaluate minimal or no fluid strategies in the resuscitation phase of sepsis.

  4. Reduced Expression of SARM in Mouse Spleen during Polymicrobial Sepsis.

    PubMed

    Gong, Yu; Zou, Lin; Cen, Dongzhi; Chao, Wei; Chen, Dunjin

    2016-12-01

    Objective Immune dysfunction, including prominent apoptosis of immune cells and decreased functioning of the remaining immune cells, plays a central role in the pathogenesis of sepsis. Sterile α and HEAT/armadillo motif-containing protein (SARM) is implicated in the regulation of immune cell apoptosis. This study aimed to elucidate SARM contributes to sepsis-induced immune cell death and immunosuppression. Methods A mouse model of polymicrobial sepsis was generated by cecum ligation and puncture (CLP). SARM gene and protein expression, caspase 3 cleavage and intracellular ATP production were measured in the mouse spleens. Results CLP-induced polymicrobial sepsis specifically attenuated both the gene and protein expression of SARM in the spleens. Moreover, the attenuation of SARM expression synchronized with splenocyte apoptosis, as evidenced by increased caspase 3 cleavage and ATP depletion. Conclusions These findings suggest that SARM is a potential regulator of sepsis-induced splenocyte apoptosis.

  5. Science review: The brain in sepsis – culprit and victim

    PubMed Central

    Sharshar, Tarek; Hopkinson, Nicholas S; Orlikowski, David; Annane, Djillali

    2005-01-01

    On one side, brain dysfunction is a poorly explored complication of sepsis. On the other side, brain dysfunction may actively contribute to the pathogenesis of sepsis. The current review aimed at summarizing the current knowledge about the reciprocal interaction between the immune and central nervous systems during sepsis. The immune-brain cross talk takes part in circumventricular organs that, being free from blood-brain-barrier, interface between brain and bloodstream, in autonomic nuclei including the vagus nerve, and finally through the damaged endothelium. Recent observations have confirmed that sepsis is associated with excessive brain inflammation and neuronal apoptosis which clinical relevance remains to be explored. In parallel, damage within autonomic nervous and neuroendocrine systems may contribute to sepsis induced organ dysfunction. PMID:15693982

  6. Oxidative Stress in Critically Ill Children with Sepsis.

    PubMed

    Wheeler, Derek S

    2011-10-07

    Sepsis is one of the leading causes of death in critically ill patients in the intensive care unit. Sepsis accounts for significant morbidity and mortality in critically ill children as well. The pathophysiology of sepsis is characterized by a complex systemic inflammatory response, endothelial dysfunction, and alterations in the coagulation system, which lead to perturbations in the delivery of oxygen and metabolic substrates to the tissues, end-organ dysfunction, and ultimately death. Oxidative stress plays a crucial role as both a promoter and mediator of the systemic inflammatory response, suggesting potential targets for the treatment of critically ill children with the sepsis syndrome. Herein, we will provide a brief review of the role of oxidative and nitrosative stress in the pathophysiology of sepsis.

  7. Therapeutic potential of HMGB1-targeting agents in sepsis

    PubMed Central

    Wang, Haichao; Zhu, Shu; Zhou, Rongrong; Li, Wei; Sama, Andrew E.

    2008-01-01

    Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. The inflammatory response is partly mediated by innate immune cells (such as macrophages, monocytes and neutrophils), which not only ingest and eliminate invading pathogens but also initiate an inflammatory response upon recognition of pathogen-associated molecular patterns (PAMPs). The prevailing theories of sepsis as a dysregulated inflammatory response, as manifested by excessive release of inflammatory mediators such as tumour necrosis factor and high-mobility group box 1 protein (HMGB1), are supported by extensive studies employing animal models of sepsis. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of experimental sepsis, and discuss the therapeutic potential of several HMGB1-targeting agents (including neutralising antibodies and steroid-like tanshinones) in experimental sepsis. PMID:18980707

  8. Role of pore-forming toxins in neonatal sepsis.

    PubMed

    Sonnen, Andreas F-P; Henneke, Philipp

    2013-01-01

    Protein toxins are important virulence factors contributing to neonatal sepsis. The major pathogens of neonatal sepsis, group B Streptococci, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus, secrete toxins of different molecular nature, which are key for defining the disease. Amongst these toxins are pore-forming exotoxins that are expressed as soluble monomers prior to engagement of the target cell membrane with subsequent formation of an aqueous membrane pore. Membrane pore formation is not only a means for immediate lysis of the targeted cell but also a general mechanism that contributes to penetration of epithelial barriers and evasion of the immune system, thus creating survival niches for the pathogens. Pore-forming toxins, however, can also contribute to the induction of inflammation and hence to the manifestation of sepsis. Clearly, pore-forming toxins are not the sole factors that drive sepsis progression, but they often act in concert with other bacterial effectors, especially in the initial stages of neonatal sepsis manifestation.

  9. 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)

  10. Immunotherapy: A promising approach to reverse sepsis-induced immunosuppression.

    PubMed

    Patil, Naeem K; Bohannon, Julia K; Sherwood, Edward R

    2016-09-01

    Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection (Third International Consensus definition for Sepsis and septic shock). Despite decades of research, sepsis remains the leading cause of death in intensive care units. More than 40 clinical trials, most of which have targeted the sepsis-associated pro-inflammatory response, have failed. Thus, antibiotics and fluid resuscitation remain the mainstays of supportive care and there is intense need to discover and develop novel, targeted therapies to treat sepsis. Both pre-clinical and clinical studies over the past decade demonstrate unequivocally that sepsis not only causes hyper-inflammation, but also leads to simultaneous adaptive immune system dysfunction and impaired antimicrobial immunity. Evidences for immunosuppression include immune cell depletion (T cells most affected), compromised T cell effector functions, T cell exhaustion, impaired antigen presentation, increased susceptibility to opportunistic nosocomial infections, dysregulated cytokine secretion, and reactivation of latent viruses. Therefore, targeting immunosuppression provides a logical approach to treat protracted sepsis. Numerous pre-clinical studies using immunomodulatory agents such as interleukin-7, anti-programmed cell death 1 antibody (anti-PD-1), anti-programmed cell death 1 ligand antibody (anti-PD-L1), and others have demonstrated reversal of T cell dysfunction and improved survival. Therefore, identifying immunosuppressed patients with the help of specific biomarkers and administering specific immunomodulators holds significant potential for sepsis therapy in the future. This review focusses on T cell dysfunction during sepsis and discusses the potential immunotherapeutic agents to boost T cell function during sepsis and improve host resistance to infection.

  11. Differential expression of plasma miR-146a in sepsis patients compared with non-sepsis-SIRS patients.

    PubMed

    Wang, Lina; Wang, Hua-Cheng; Chen, Cha; Zeng, Jianming; Wang, Qian; Zheng, Lei; Yu, Huan-DU

    2013-04-01

    Sepsis is a subtype of systemic inflammatory response syndrome (SIRS), which is characterized by infection. Circulating microRNAs (miRNAs), including miR-150, miR-146a and miR-223, are potential biomarkers of sepsis. In this study, we demonstrated that measuring the relative expression of miR-146a/U6 in plasma, using the 2(-ΔΔCt) method, provides a method for differentiating between sepsis and non-sepsis-SIRS. We observed a significant increase in miR-146a expression in the initial cohort of 6 non-sepsis-SIRS patients compared to the 4 sepsis patients (P=0.01) and in the second cohort of 8 non-sepsis-SIRS patients compared to the 10 sepsis patients (P=0.027). Additionally, we identified that sodium citrate and ethylenediaminetetraacetic acid (EDTA) K2 may be used as anticoagulant reagents. Generation of a standard curve is not necessary in these diagnostic tests, unless the standard of normalization is carefully selected. Thus we provide more detailed guidance for the clinical use of circulating miRNA biomarkers.

  12. Hypomagnesemia in Critically Ill Sepsis Patients.

    PubMed

    Velissaris, Dimitrios; Karamouzos, Vassilios; Pierrakos, Charalampos; Aretha, Diamanto; Karanikolas, Menelaos

    2015-12-01

    Magnesium (Mg), also known as "the forgotten electrolyte", is the fourth most abundant cation overall and the second most abundant intracellular cation in the body. Mg deficiency has been implicated in the pathophysiology of many diseases. This article is a review of the literature regarding Mg abnormalities with emphasis on the implications of hypomagnesemia in critical illness and on treatment options for hypomagnesemia in critically ill patients with sepsis. Hypomagnesemia is common in critically ill patients, and there is strong, consistent clinical evidence, largely from observational studies, showing that hypomagnesemia is significantly associated with increased need for mechanical ventilation, prolonged ICU stay and increased mortality. Although the mechanism linking hypomagnesemia with poor clinical outcomes is not known, experimental data suggest mechanisms contributing to such outcomes. However, at the present time, there is no clear evidence that magnesium supplementation improves outcomes in critically ill patients with hypomagnesemia. Large, well-designed clinical trials are needed to evaluate the role of magnesium therapy for improving outcomes in critically ill patients with sepsis.

  13. 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.

  14. Peripheral muscle dysfunction in COPD: lower limbs versus upper limbs.

    PubMed

    Miranda, Eduardo Foschini; Malaguti, Carla; Corso, Simone Dal

    2011-01-01

    In patients with COPD, the degree of functional impairment appears to differ between the upper and lower limbs. Significant dyspnea and fatigue have been reported by these patients when performing tasks with unsupported upper limbs and two mechanisms have been proposed to explain this fact: neuromechanical dysfunction of respiratory muscles; and changes in lung volume during such activities. The neuromechanical dysfunction seen in COPD patients during this type of exercise is related to changes in the breathing pattern, as well as to the simultaneity of afferent and efferent muscle stimuli, resulting in respiratory muscle asynchrony. In addition, the increased ventilation during upper limb exercise in patients with COPD leads to dynamic hyperinflation at different workloads. During lower limb exercises, the strength and endurance of the quadriceps muscle is lower in COPD patients than in healthy subjects. This could by explained by abnormal muscle metabolism (decreased aerobic capacity), dependence on glycolytic metabolism, and rapid accumulation of lactate during exercise. In comparison with lower limb exercises, upper limb exercises result in higher metabolic and ventilatory demands, as well as in a more intense sensation of dyspnea and greater fatigue. Because there are differences between the upper and lower limb muscles in terms of the morphological and functional adaptations in COPD patients, specific protocols for strength training and endurance should be developed and tested for the corresponding muscle groups.

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

    PubMed Central

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

    2014-01-01

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

  16. 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

  17. Challenges in the diagnosis and management of neonatal sepsis.

    PubMed

    Zea-Vera, Alonso; Ochoa, Theresa J

    2015-02-01

    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.

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

    PubMed

    Shah, Birju A; Padbury, James F

    2014-01-01

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

  19. Diagnosis trajectories of prior multi-morbidity predict sepsis mortality

    PubMed Central

    Beck, Mette K.; Jensen, Anders Boeck; Nielsen, Annelaura Bach; Perner, Anders; Moseley, Pope L.; Brunak, Søren

    2016-01-01

    Sepsis affects millions of people every year, many of whom will die. In contrast to current survival prediction models for sepsis patients that primarily are based on data from within-admission clinical measurements (e.g. vital parameters and blood values), we aim for using the full disease history to predict sepsis mortality. We benefit from data in electronic medical records covering all hospital encounters in Denmark from 1996 to 2014. This data set included 6.6 million patients of whom almost 120,000 were diagnosed with the ICD-10 code: A41 ‘Other sepsis’. Interestingly, patients following recurrent trajectories of time-ordered co-morbidities had significantly increased sepsis mortality compared to those who did not follow a trajectory. We identified trajectories which significantly altered sepsis mortality, and found three major starting points in a combined temporal sepsis network: Alcohol abuse, Diabetes and Cardio-vascular diagnoses. Many cancers also increased sepsis mortality. Using the trajectory based stratification model we explain contradictory reports in relation to diabetes that recently have appeared in the literature. Finally, we compared the predictive power using 18.5 years of disease history to scoring based on within-admission clinical measurements emphasizing the value of long term data in novel patient scores that combine the two types of data. PMID:27812043

  20. Activated Complement Factors as Disease Markers for Sepsis

    PubMed Central

    Charchaflieh, Jean; Rushbrook, Julie; Worah, Samrat; Zhang, Ming

    2015-01-01

    Sepsis is a leading cause of death in the United States and worldwide. Early recognition and effective management are essential for improved outcome. However, early recognition is impeded by lack of clinically utilized biomarkers. Complement factors play important roles in the mechanisms leading to sepsis and can potentially serve as early markers of sepsis and of sepsis severity and outcome. This review provides a synopsis of recent animal and clinical studies of the role of complement factors in sepsis development, together with their potential as disease markers. In addition, new results from our laboratory are presented regarding the involvement of the complement factor, mannose-binding lectin, in septic shock patients. Future clinical studies are needed to obtain the complete profiles of complement factors/their activated products during the course of sepsis development. We anticipate that the results of these studies will lead to a multipanel set of sepsis biomarkers which, along with currently used laboratory tests, will facilitate earlier diagnosis, timely treatment, and improved outcome. PMID:26420913

  1. Characterising Cytokine Gene Expression Signatures in Patients with Severe Sepsis

    PubMed Central

    Grealy, Robert; White, Mary; Stordeur, Patrick; Kelleher, Dermot; Doherty, Derek G.; McManus, Ross; Ryan, Thomas

    2013-01-01

    Introduction. Severe sepsis in humans may be related to an underlying profound immune suppressive state. We investigated the link between gene expression of immune regulatory cytokines and the range of illness severity in patients with infection and severe sepsis. Methods. A prospective observational study included 54 ICU patients with severe sepsis, 53 patients with infection without organ failure, and 20 healthy controls. Gene expression in peripheral blood mononuclear cells (PBMC) was measured using real-time polymerase chain reaction. Results. Infection differed from health by decreased expression of the IL2, and IL23 and greater expression of IL10 and IL27. Severe sepsis differed from infection by having decreased IL7, IL23, IFNγ, and TNFα gene expression. An algorithm utilising mRNA copy number for TNFα, IFNγ, IL7, IL10, and IL23 accurately distinguished sepsis from severe sepsis with a receiver operator characteristic value of 0.88. Gene expression was similar with gram-positive and gram-negative infection and was similar following medical and surgical severe sepsis. Severity of organ failure was associated with serum IL6 protein levels but not with any index of cytokine gene expression in PBMCs. Conclusions. Immune regulatory cytokine gene expression in PBMC provides a robust method of modelling patients' response to infection. PMID:23935244

  2. Colloids in sepsis: evenly distributed molecules surrounded by uneven questions.

    PubMed

    Zampieri, Fernando Godinho; Park, Marcelo; Azevedo, Luciano Cesar Pontes

    2013-05-01

    Colloids are frequently used for fluid expansion in the intensive care unit, although its use on several clinical scenarios remains unproven of any relevant clinical benefit. The purpose of this article was to carry out a narrative review regarding the safety and efficacy of colloids in patients with sepsis and septic shock, with emphasis on the most commonly used colloids, albumin and starches. Colloids are effective fluid expanders and are able to restore the hemodynamic profile with less total volume than crystalloids. These properties appear to be preserved even in patients with sepsis with increased capillary permeability. However, some colloids are associated with renal impairment and coagulation abnormalities. Starch use was associated with increased mortality in two large clinical trials. Also, starches probably have significant renal adverse effects and may be related to more need for renal replacement therapy in severe sepsis. Albumin is the only colloid that has been shown safe in patients with sepsis and that may be associated with improved outcomes on specific subpopulations. No trial so far found any robust clinical end point favoring colloid use in patients with sepsis. Because there is no proven benefit of the use of most colloids in patients with sepsis, its use should not be encouraged outside clinical trials. Albumin is the only colloid solution that has proven to be safe, and its use may be considered on hypoalbuminemic patients with sepsis. Nevertheless, there are no robust data to recommend routine albumin administration in sepsis. Starch use should be avoided in patients with sepsis because of the recent findings of a multicenter randomized study until further evidence is available.

  3. Simulation of Upper Limb Movements

    NASA Astrophysics Data System (ADS)

    Uherčík, Filip; Hučko, Branislav

    2011-12-01

    The paper deals with controlling an upper limb prosthesis based on the measurement of myoelectric signals (MES) while drinking. MES signals have been measured on healthy limbs to obtain the same response for the prosthesis. To simulate the drinking motion of a healthy upper limb, the program ADAMS was used, with all degrees of freedom and a hand after trans-radial amputation with an existing hand prosthesis. Modification of the simulation has the exact same logic of control, where the muscle does not have to be strenuous all the time, but it is the impulse of the muscle which drives the motor even though the impulse disappears and passed away.

  4. 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

  5. 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…

  6. Accurate coding in sepsis: clinical significance and financial implications.

    PubMed

    Chin, Y T; Scattergood, N; Thornber, M; Thomas, S

    2016-09-01

    Sepsis is a major healthcare problem and leading cause of death worldwide. UK hospital mortality statistics and payments for patient episodes of care are calculated on clinical coding data. The accuracy of these data depends on the quality of coding. This study aimed to investigate whether patients with significant bacteraemia are coded for sepsis and to estimate the financial costs of miscoding. Of 54 patients over a one-month period with a significant bacteraemia, only 19% had been coded for sepsis. This is likely to lead to falsely high calculated hospital mortality. Furthermore, this resulted in an underpayment of £21,000 for one month alone.

  7. Challenges with Diagnosing and Managing Sepsis in Older Adults

    PubMed Central

    Clifford, Kalin M.; Dy-Boarman, Eliza A.; Haase, Krystal K.; Maxvill, Kristen (Hesch); Pass, Steven; Alvarez, Carlos A.

    2016-01-01

    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 as well as offers recommendations for monitoring and treating sepsis in the older adult population. PMID:26687340

  8. Sepsis-associated takotsubo cardiomyopathy can be reversed with levosimendan.

    PubMed

    Karvouniaris, Marios; Papanikolaou, John; Makris, Demosthenes; Zakynthinos, Epameinondas

    2012-06-01

    Sepsis is a stressful physical condition, and at the acute phase, overstimulation of the sympathetic nervous system may occur; these events have the potential to induce cardiomyopathy. Takotsubo cardiomyopathy (TTC) is a form of catecholamine-induced cardiomyopathy, which occurs very rarely in sepsis. However, TTC management in critically ill patients with sepsis may be challenging because the use of exogenous catecholamines for circulatory support might augment further TTC. Herein, we report a rare case of TTC after urosepsis; and we point out that cardiac function may improve after catecholamine withdrawal and the application of calcium channel sensitizer levosimendan.

  9. The Physiology of Early Goal-Directed Therapy for Sepsis.

    PubMed

    Lief, Lindsay; Arbo, John; Berlin, David A

    2016-10-05

    In 2001, Rivers and colleagues published a randomized controlled trial of early goal-directed therapy (EGDT) for the treatment of sepsis. More than a decade later, it remains a landmark achievement. The study proved the benefits of early aggressive treatment of sepsis. However, many questions remain about specific aspects of the complex EGDT algorithm. Recently, 3 large trials attempted to replicate these results. None of the studies demonstrated a benefit of an EGDT protocol for sepsis. This review explores the physiologic basis of goal-directed therapy, including the hemodynamic targets and the therapeutic interventions. An understanding of the physiologic basis of EGDT helps reconcile the results of the clinical trials.

  10. Nutritional support in sepsis: still skeptical?

    PubMed

    Nitenberg, Gérard

    2000-08-01

    The immediate metabolic response to a septic challenge is probably adaptive, meaning that nutritional interference, mainly via the parenteral route, during this early phase of instability can do more harm than good. During the later phases, a gradual increase in enteral nutrition, at the expense of parenteral nutrition, combined with the administration of nutraceuticals such as glutamine and omega-3 fatty acids, can counteract wasting and modulate the complex inflammatory response and immunosuppression associated with sepsis. In these times of scarce resources, there is an urgent need to clearly document the efficacy of immuno/pharmaconutrients, individually and in combination, enterally or parenterally, before proposing them for routine management of septic patients in the intensive care unit.

  11. Sepsis, parenteral vaccination and skin disinfection

    PubMed Central

    Cook, Ian F.

    2016-01-01

    ASBSTRACT Disinfection should be required for all skin penetrative procedures including parenteral administration of vaccines. This review analyses medically attended infectious events following parenteral vaccination in terms of their microbiological aetiology and pathogenesis. Like ‘clean’ surgical site infections, the major pathogens responsible for these events were Staphylococcal species, implicating endogenous con-tamination as a significant source of infection. As 70% isopropyl alcohol swabbing has been shown to effectively disinfect the skin, it would be medico-legally difficult to defend a case of sepsis with the omission of skin disinfection unless the very low risk of this event was adequately explained to the patient and documented prior to vaccination. There was a significant cost-benefit for skin disinfection and cellulitis. Skin disinfection in the context of parenteral vaccination represents a new paradigm of medical practice; the use of a low cost intervention to prevent an event of very low prevalence but of significant cost. PMID:27295449

  12. An Immunological Perspective on Neonatal Sepsis

    PubMed Central

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

    2016-01-01

    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

  13. Sepsis: from pattern to mechanism and back.

    PubMed

    An, Gary; Namas, Rami A; Vodovotz, Yoram

    2012-01-01

    Sepsis is a clinical entity in which complex inflammatory and physiological processes are mobilized, not only across a range of cellular and molecular interactions, but also in clinically relevant physiological signals accessible at the bedside. There is a need for a mechanistic understanding that links the clinical phenomenon of physiologic variability with the underlying patterns of the biology of inflammation, and we assert that this can be facilitated through the use of dynamic mathematical and computational modeling. An iterative approach of laboratory experimentation and mathematical/computational modeling has the potential to integrate cellular biology, physiology, control theory, and systems engineering across biological scales, yielding insights into the control structures that govern mechanisms by which phenomena, detected as biological patterns, are produced. This approach can represent hypotheses in the formal language of mathematics and computation, and link behaviors that cross scales and domains, thereby offering the opportunity to better explain, diagnose, and intervene in the care of the septic patient.

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

    PubMed

    Karima, Risuke

    2008-03-01

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

  15. 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.

  16. Inhibited muscle amino acid uptake in sepsis.

    PubMed Central

    Hasselgren, P O; James, J H; Fischer, J E

    1986-01-01

    Amino acid uptake in vivo was determined in soleus (SOL) muscle, diaphragm, heart, and liver following intravenous injection of [3H]-alpha-amino-isobutyric acid ([3H]-AIB) in rats made septic by cecal ligation and puncture (CLP) and in sham-operated controls. Muscle amino acid transport was also measured in vitro by determining uptake of [3H]-AIB in incubated extensor digitorum longus (EDL) and SOL muscles. Results were expressed as distribution ratio between [3H]-AIB in intracellular and extracellular fluid. AIB uptake in vivo was reduced by 90% in SOL and cardiac muscle and by 45% in diaphragm 16 hours after CLP. In contrast, AIB uptake by liver was almost four times higher in septic than in control animals. AIB uptake in vitro was reduced by 18% in EDL 8 hours after CLP but was not significantly altered in SOL at the same time point. Sixteen hours after CLP, AIB uptake was significantly reduced in both muscles, i.e., by 17% in EDL and by 65% in SOL. When muscles from untreated rats were incubated in the presence of plasma from septic animals (16 hours CLP) or from animals injected with endotoxin (2 mg/kg body weight), AIB uptake was reduced. Addition of endotoxin in vitro (2-200 micrograms/ml) to incubated muscles did not affect AIB uptake. The results suggest that sepsis leads to marked impairment of amino acid transport system A in muscle and that this impairment is mediated by a circulating factor that is not endotoxin. Reduced uptake of amino acids by skeletal muscle during sepsis may divert amino acids to the liver for increased gluconeogenesis and protein synthesis. PMID:3963895

  17. 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

  18. Limb displacement and brightness seismology

    NASA Astrophysics Data System (ADS)

    Emilio, Marcelo; Cunnyngham, Ian; Kuhn, Jeff; Mehret, Leandro; Bush, Rock; Scholl, Isabelle

    2015-08-01

    The Helioseismic and Magnetic Imager (HMI) abord the Solar Dynamics Observatory (SDO) has been used to obtain the most sensitive spectrally resolved observation of individual p-modes at the extreme solar limb. Such oscillation observations of the limb displacement and brightness for some spatial and temporal regimes are even competitive in signal-to-noise to full-disk doppler measurements of the p-mode spectrum. Limb measurements of 5-min p-modes, while having many similarities to full-disk doppler observations, have significantly different sensitivities to the solar rotation and the 5-min mode solar atmospheric structure. These may provide information about the solar structure which is complementary to full-disk measurements. In this work we present results from Individual spherical harmonic p-modes that were detected around solar limb with amplitudes at the micro-arcsecond level.

  19. Performance of Interleukin-27 as a Sepsis Diagnostic Biomarker in Critically Ill Adults

    PubMed Central

    Wong, Hector R.; Liu, Kathleen D.; Kangelaris, Kirsten N.; Lahni, Patrick; Calfee, Carolyn S.

    2014-01-01

    Purpose We recently identified interleukin-27 (IL-27) as a sepsis diagnostic biomarker in children. Here we assess IL-27 as a sepsis diagnostic biomarker in critically ill adults with systemic inflammatory response syndrome (SIRS) and sepsis. Methods IL-27 and procalcitonin (PCT) were measured from plasma samples in three groups: no sepsis (n = 78), pulmonary source of sepsis (n = 66), and non-pulmonary source of sepsis (n = 43). Receiver operating characteristic curves and classification and regression tree methodology were used to evaluate biomarker performance. Results IL-27 did not discriminate effectively between sepsis and sterile SIRS in unselected patients. The highest area under the curve (AUC) was 0.70 (95% C.I. 0.60 – 0.80) for IL-27 in subjects with a non-pulmonary source of sepsis. A decision tree incorporating IL-27, PCT, and age had an AUC of 0.79 (0.71 – 0.87) in subjects with a non-pulmonary source of sepsis. Compared to children with sepsis, adults with sepsis express less IL-27. Conclusions IL-27 performed overall poorly in this cohort as a sepsis diagnostic biomarker. Combining IL-27, PCT, and age reasonably estimated the risk of sepsis in subjects with a non-pulmonary source of sepsis. IL-27 may be a more reliable sepsis diagnostic biomarker in children than in adults. PMID:24848949

  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.

  1. Picroside II protects against sepsis via suppressing inflammation in mice

    PubMed Central

    Huang, Ying; Zhou, Miao; Li, Chengbao; Chen, Yuanli; Fang, Wei; Xu, Guo; Shi, Xueyin

    2016-01-01

    Picroside II, an iridoid compound extracted from Picrorhiza, exhibits anti-inflammatory and anti-apoptotic activities. We explored the protective effects and mechanisms of picroside II in a mouse model of sepsis induced by cecal ligation and puncture (CLP), using three groups of mice: Group A (sham), Group B (CLP+NS) and Group C (CLP+20 mg/kg picroside II). The mortality in mice with sepsis was decreased by the administration of picroside II, and lung injury was alleviated simultaneously. Picroside II treatment enhanced bacterial clearance in septic mice. Further, picroside II treatment alleviated the inflammatory response in sepsis and enhanced immune function by inhibiting the activation of NLRP3 inflammasome and NF-κB pathways. Picroside II may represent an anti-inflammatory drug candidate, providing novel insight into the treatment of sepsis. PMID:28078023

  2. Use of biomarkers in pediatric sepsis: literature review

    PubMed Central

    Lanziotti, Vanessa Soares; Póvoa, Pedro; Soares, Márcio; Silva, José Roberto Lapa e; Barbosa, Arnaldo Prata; Salluh, Jorge Ibrain Figueira

    2016-01-01

    Despite advances in recent years, sepsis is still a leading cause of hospitalization and mortality in infants and children. The presence of biomarkers during the response to an infectious insult makes it possible to use such biomarkers in screening, diagnosis, prognosis (risk stratification), monitoring of therapeutic response, and rational use of antibiotics (for example, the determination of adequate treatment length). Studies of biomarkers in sepsis in children are still relatively scarce. This review addresses the use of biomarkers in sepsis in pediatric patients with emphasis on C-reactive protein, procalcitonin, interleukins 6, 8, and 18, human neutrophil gelatinase, and proadrenomedullin. Assessment of these biomarkers may be useful in the management of pediatric sepsis. PMID:28099644

  3. HDL in sepsis - risk factor and therapeutic approach.

    PubMed

    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.

  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.

  5. Government introduces action plan to reduce deaths from sepsis.

    PubMed

    Kleebauer, Alistair

    2015-01-20

    Tackling sepsis - the potentially fatal over-reaction of the immune system to infection - must be given the same priority as reducing Clostridium difficile and MRSA infections, the government has said.

  6. Histamine H3 activation depresses cardiac function in experimental sepsis.

    PubMed

    Li, X; Eschun, G; Bose, D; Jacobs, H; Yang, J J; Light, R B; Mink, S N

    1998-11-01

    In the heart, histamine (H3) receptors may function as inhibitory presynaptic receptors that decrease adrenergic norepinephrine release in conditions of enhanced sympathetic neural activity. We hypothesized that H3-receptor blockade might improve cardiovascular function in sepsis. In a canine model of Escherichia coli sepsis, we found that H3-receptor blockade increased cardiac output (3.6 to 5.3 l/min, P < 0.05), systemic blood pressure (mean 76 to 96 mmHg, P < 0.05), and left ventricular contractility compared with pretreatment values. Plasma histamine concentrations increased modestly in the H3-blocker-sepsis group compared with values obtained in a nonsepsis-time-control group. In an in vitro preparation, histamine H3 activation could be identified under conditions of septic plasma. We conclude that activation of H3 receptors may contribute to cardiovascular collapse in sepsis.

  7. Clinical Decision Support for Early Recognition of Sepsis.

    PubMed

    Amland, Robert C; Hahn-Cover, Kristin E

    2016-01-01

    Sepsis is an inflammatory response triggered by infection, with a high in-hospital mortality rate. Early recognition and treatment can reverse the inflammatory response, with evidence of improved patient outcomes. One challenge clinicians face is identifying the inflammatory syndrome against the background of the patient's infectious illness and comorbidities. An approach to this problem is implementation of computerized early warning tools for sepsis. This multicenter retrospective study sought to determine clinimetric performance of a cloud-based computerized sepsis clinical decision support system (CDS), understand the epidemiology of sepsis, and identify opportunities for quality improvement. Data encompassed 6200 adult hospitalizations from 2012 through 2013. Of 13% patients screened-in, 51% were already suspected to have an infection when the system activated. This study focused on a patient cohort screened-in before infection was suspected; median time from arrival to CDS activation was 3.5 hours, and system activation to diagnostic collect was another 8.6 hours.

  8. 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.

  9. Sepsis in cirrhosis: emerging concepts in pathogenesis, diagnosis and management.

    PubMed

    Philips, Cyriac Abby; Sarin, Shiv Kumar

    2016-11-01

    Infections and sepsis are more common in cirrhotic than in the general population and constitute the commonest cause of sudden worsening and death. The diagnosis of systemic inflammatory syndrome and sepsis are challenging in cirrhotics due to an underlying a state of hyperdynamic circulation. Further, poor nutritional and bone marrow reserves lead to modest host immune response, the so called immunoparalysis state and the outcome of antibiotic therapy is suboptimal. In this review, a comprehensive description of current and emerging concepts in the pathogenesis and diagnosis of sepsis with importance to current and novel biomarkers for diagnosis of sepsis in cirrhosis is presented. Furthermore, novel treatment options and preventive strategies are discussed to improve the overall survival.

  10. 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

  11. 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

  12. A new integrated technique for the supportive treatment of sepsis.

    PubMed

    Hartmann, Jens; Harm, Stephan

    2017-03-06

    Although there has been continuous, intensive research for many years in the field of sepsis treatment, currently available treatment options are limited, and there is still a lack of systems that efficiently remove endotoxins as well as mediators. Here, we discuss a newly developed, integrated technique that combines different aspects for their use in extracorporeal blood purification for the supportive treatment of liver failure and sepsis.

  13. Early diagnosis of sepsis using serum hemoglobin subunit Beta.

    PubMed

    Yoo, Hayoung; Ku, Sae-Kwang; Kim, Shin-Woo; Bae, Jong-Sup

    2015-02-01

    The development of new sepsis-specific biomarkers is mandatory to improve the detection and monitoring of the disease. Hemoglobin is the main oxygen and carbon dioxide carrier in cells of the erythroid lineage and is responsible for oxygen delivery to the respiring tissues of the body. Hemoglobin subunit beta (HBβ) is a component of a larger protein called hemoglobin. The aim of this study was to evaluate blood levels of HBβ in septic patients. A prospective study of 82 patients with sepsis was conducted. Furthermore, C57BL/6 mice were subjected to cecal ligation and puncture (CLP) surgery. Alternatively, human umbilical vein endothelial cells (HUVECs) or C57BL/6 mice were exposed to lipopolysaccharide (LPS, 100 ng/ml to HUVECs or 10 mg/kg to mice). The data showed that LPS induced upregulation of the synthesis and secretion of HBβ in LPS-treated HUVECs and in LPS-injected and CLP mice. In patients admitted to the intensive care unit with sepsis, circulating levels of HBβ were significantly high (sepsis, 64.93-114.76 ng/ml, n = 30; severe sepsis, 157.37-268.69 ng/ml, n = 22; septic shock, 309.98-427.03 ng/ml, n = 30) when compared to the levels of control donors (9.76-12.28 ng/ml, n = 21). Patients with septic shock had higher HBβ levels when compared to patients with severe sepsis. Furthermore, the HBβ levels in septic patients were higher than those in healthy volunteers. These results suggest that in septic patients, HBβ blood level is related to the severity of sepsis and may represent a novel endothelial cell dysfunction marker. Moreover, HBβ can be used as a biomarker to determine the severity of sepsis.

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

    PubMed

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

    2014-08-21

    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.

  15. A Review of GM-CSF Therapy in Sepsis

    PubMed Central

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

    2015-01-01

    Abstract 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

  16. Role of Exogenous Hsp72 on Liver Dysfunction during Sepsis.

    PubMed

    Tsai, Tsen-Ni; Ho, Jia-Jing; Liu, Maw-Shung; Lee, Tzu-Ying; Lu, Mei-Chin; Liu, Chia-Jen; Huang, Li-Ju; Lue, Sheng-I; Yang, Rei-Chen

    2015-01-01

    This study examined the role of exogenous heat shock protein 72 (Hsp72) in reversing sepsis-induced liver dysfunction. Sepsis was induced by cecal ligation and puncture. Liver function was determined on the basis of the enzymatic activities of serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT). Apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and caspase-9, and cleaved poly (ADP-ribose) polymerase (PARP) protein expressions were analyzed using Western blotting. Results showed GOT and GPT levels increased during sepsis, and levels were restored following the administration of human recombinant Hsp72 (rhHsp72). Increased liver tissue apoptosis was observed during sepsis, and normal apoptosis resumed on rhHsp72 administration. The Bcl-2/Bax ratio, cleaved caspase-3, caspase-9, and PARP protein expressions in the liver tissues were upregulated during sepsis and normalized after rhHsp72 treatment. We conclude that, during sepsis, exogenous Hsp72 restored liver dysfunction by inhibiting apoptosis via the mitochondria-initiated caspase pathway.

  17. Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis

    PubMed Central

    Lee, Sang Hoon; Park, Moo Suk; Park, Byung Hoon; Jung, Won Jai; Lee, In Seon; Kim, Song Yee; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Kim, Young Sam; Kim, Se Kyu; Chang, Joon; Chung, Kyung Soo

    2015-01-01

    Background. Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations. Methods. We evaluated 117 patients with sepsis (severe sepsis [n = 19] and septic shock [n = 98]) who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acid (FFA), and apolipoprotein (Apo) A-I levels were measured on days 0, 1, 3, and 7. Results. Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (p = 0.043, p = 0.020, p = 0.005, and p = 0.015, resp.). According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 (p = 0.018 and p = 0.008, resp.). Conclusions. Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients. PMID:26351639

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. Current trends in inflammatory and immunomodulatory mediators in sepsis

    PubMed Central

    Aziz, Monowar; Jacob, Asha; Yang, Weng-Lang; Matsuda, Akihisa; Wang, Ping

    2013-01-01

    Sepsis refers to severe systemic inflammation in response to invading pathogens. An overwhelming immune response, as mediated by the release of various inflammatory mediators, can lead to shock, multiple organ damage, and even death. Cytokines, proteases, lipid mediators, gaseous substances, vasoactive peptides, and cell stress markers play key roles in sepsis pathophysiology. Various adhesion molecules and chemokines sequester and activate neutrophils into the target organs, further augmenting inflammation and tissue damage. Although the anti-inflammatory substances counterbalance proinflammatory mediators, prolonged immune modulation may cause host susceptibility to concurrent infections, thus reflecting enormous challenge toward developing effective clinical therapy against sepsis. To understand the complex interplay between pro- and anti-inflammatory phenomenon in sepsis, there is still an unmet need to study newly characterized mediators. In addition, revealing the current trends of novel mediators will upgrade our understanding on their signal transduction, cross-talk, and synergistic and immunomodulating roles during sepsis. This review highlights the latest discoveries of the mediators in sepsis linking to innate and adaptive immune systems, which may lead to resolution of many unexplored queries. PMID:23136259

  4. HMGB1 mediates anemia of inflammation in murine sepsis survivors.

    PubMed

    Valdés-Ferrer, Sergio I; Papoin, Julien; Dancho, Meghan E; Olofsson, Peder; 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

    2015-12-29

    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 TNF and IL-6 are elevated for five days after the onset of sepsis, and serum HMGB1 levels are increased from day seven until at least day 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±1.7g/dL versus 11.7±1.2g/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.

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

    PubMed

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

    2016-03-09

    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.

  6. Immunotherapy of Sepsis: Blind Alley or Call for Personalized Assessment?

    PubMed

    Prucha, Miroslav; Zazula, Roman; Russwurm, Stefan

    2017-02-01

    Sepsis is the most frequent cause of death in noncoronary intensive care units. In the past 10 years, progress has been made in the early identification of septic patients and their treatment. These improvements in support and therapy mean that mortality is gradually decreasing, however, the rate of death from sepsis remains unacceptably high. Immunotherapy is not currently part of the routine treatment of sepsis. Despite experimental successes, the administration of agents to block the effect of sepsis mediators failed to show evidence for improved outcome in a multitude of clinical trials. The following survey summarizes the current knowledge and results of clinical trials on the immunotherapy of sepsis and describes the limitations of our knowledge of the pathogenesis of sepsis. Administration of immunomodulatory drugs should be linked to the current immune status assessed by both clinical and molecular patterns. Thus, a careful daily review of the patient's immune status needs to be introduced into routine clinical practice giving the opportunity for effective and tailored use of immunomodulatory therapy.

  7. 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

  8. Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model.

    PubMed

    Aare, Sudhakar; Ochala, Julien; Norman, Holly S; Radell, Peter; Eriksson, Lars I; Göransson, Hanna; Chen, Yi-Wen; Hoffman, Eric P; Larsson, Lars

    2011-12-16

    Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients that is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents, corticosteroids (CS), and sepsis for 5 days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after 5 days' exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to 5 days' exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle-specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements, and sarcomeric proteins underlying the relative sparing of cranial vs. spinal nerve innervated muscles during exposure to the ICU intervention.

  9. Cross-limb vascular shunting for major limb replantation.

    PubMed

    Lee, Yao-Chou; Lee, Jing-Wei

    2009-02-01

    In the management of traumatic major limb amputation, rapid re-establishment of circulation to the amputated part is imperative so as to prevent complications related to reperfusion injury, especially for those already suffering from prolonged ischemia. A temporary, extra-anatomic cross limb shunting with infusion lines can be used to perfuse the amputated part almost instantaneously. This allows the surgeon to carry out skeletal fixation and other reparative works in an unhurried manner. The cannulation site is targeted at intact vessels far away from the injury zone, obviating the need to explore and handle traumatized vessels at the mangled stump ends, thus greatly simplifying and expediting the revascularization process. Such a method had been successfully applied in 2 young people suffering traumatic arm amputation and thigh amputation, respectively. We suggested that such a procedure could be a useful adjunct in the field of major limb replantation.

  10. Early sepsis does not increase the risk of late sepsis in very low birth weight neonates

    PubMed Central

    Wynn, James L.; Hansen, Nellie I.; Das, Abhik; Cotten, C. Michael; Goldberg, Ronald N.; Sánchez, Pablo J.; Bell, Edward F.; Van Meurs, Krisa P.; Carlo, Waldemar A.; Laptook, Abbot R.; Higgins, Rosemary D.; Benjamin, Daniel K.; Stoll, Barbara J.

    2012-01-01

    Objective To examine whether preterm very low birth weight (VLBW) infants have an increased risk of late-onset sepsis (LOS) following early-onset sepsis (EOS). Study design Retrospective analysis of VLBW infants (401-1500 g) born September 1998 through December 2009 who survived >72 hours and were cared for within the NICHD Neonatal Research Network. Sepsis was defined by growth of bacteria or fungi in a blood culture obtained ≤72 hr of birth (EOS) or >72 hr (LOS) and antimicrobial therapy for ≥5 days or death <5 d while receiving therapy. Regression models were used to assess risk of death or LOS by 120d and LOS by 120d among survivors to discharge or 120d, adjusting for gestational age and other covariates. Results Of 34,396 infants studied 504 (1.5%) had EOS. After adjustment, risk of death or LOS by 120d did not differ overall for infants with EOS compared with those without EOS [RR:0.99 (0.89-1.09)] but was reduced in infants born at <25wk gestation [RR:0.87 (0.76-0.99), p=0.048]. Among survivors, no difference in LOS risk was found overall for infants with versus without EOS [RR:0.88 (0.75-1.02)], but LOS risk was shorter in infants with BW 401-750 g who had EOS [RR:0.80 (0.64-0.99), p=0.047]. Conclusions Risk of LOS after EOS was not increased in VLBW infants. Surprisingly, risk of LOS following EOS appeared to be reduced in the smallest, most premature infants, underscoring the need for age-specific analyses of immune function. PMID:23295144

  11. 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.

  12. Surgical Critical Care for the Patient with Sepsis and Multiple Organ Dysfunction.

    PubMed

    Kaml, Gary J; Davis, Kimberly A

    2016-12-01

    Sepsis and multiple organ dysfunction syndrome (MODS) is common in the surgical intensive care unit. Sepsis involves infection and the patient's immune response. Timely recognition of sepsis and swift application of evidence-based interventions is critical to the success of therapy. This article reviews the nature of the septic process, existing definitions of sepsis, and current evidence-based treatment strategies for sepsis and MODS. An improved understanding of the process of sepsis and its relation to MODS has resulted in clinical definitions and scoring systems that allow for the quantification of disease severity and guidelines for treatment.

  13. [Immune monitoring in SIRS and sepsis based on the PIRO model].

    PubMed

    Meisel, C; Höflich, C; Volk, H-D

    2008-11-01

    Sepsis is a life-threatening disease characterized by a complex interaction between pathogens and the immune system. The analysis of immune parameters in patients with sepsis or at risk for sepsis may help to identify predisposing factors and infection-specific reaction patterns, as well as to monitor the current functional state of the immune system. This may lead to personalized therapeutic strategies for improving outcome in sepsis. Based on the PIRO model (predisposition, insult, response, organ dysfunction), a pathophysiologically-oriented concept for the development of a new sepsis classification, this article reviews currently used and new parameters for immunomonitoring in SIRS (systemic inflammatory response syndrome) and sepsis.

  14. Neonatal sepsis and multiple skin abscess in a newborn with Down's syndrome: A case report.

    PubMed

    Kali, Arunava; Sivaraman, Umadevi; Sreenivasan, Srirangaraj; Stephen, Selvaraj

    2013-01-01

    Neonatal sepsis is a leading cause of neonatal mortality. Congenital heart disease accounts for additional risk of sepsis in neonates. Here we report a case of Down's syndrome with late onset neonatal sepsis associated with multiple superficial skin abscesses simulating staphylococcal infection. The baby was empirically treated with vancomycin. Subsequently, multidrug resistant Klebsiella pneumoniae was detected from both pus and blood culture. Change to appropriate antibiotic resulted in clinical recovery. Although sepsis is one of the major ailments in neonates, atypical presentations of neonatal sepsis in Down's syndrome patients are underreported. Here we highlight the atypical presentation of Klebsiella sepsis and the importance of early antibiogram in such cases.

  15. Energy metabolism in sepsis and injury.

    PubMed

    Chioléro, R; Revelly, J P; Tappy, L

    1997-09-01

    The development of malnutrition is often rapid in critically ill patients with sepsis and severe trauma. In such patients, a wide array of hormonal and nonhormonal mediators are released, inducing complex metabolic changes. Hypermetabolism, associated with protein and fat catabolism, negative nitrogen balance, hyperglycemia, and resistance to insulin, constitute the hallmark of this response. Critically ill patients demonstrate a marked alteration in the adaptation to prolonged starvation: resting metabolic rate and tissue catabolism stay elevated, while ketogenesis remains suppressed. The response to nutrition support is impaired. Substrate use is modified in septic and traumatized patients. Glucose administration during severe aggression does not suppress the enhanced hepatic glucose production and the lipolysis. This phenomenon, related to tissue insulin resistance, ensures a high flow of glucose to the predominantly glucose-consuming cells, such as the wound, the inflammatory, and immune cells, all insulin-independent cells. In addition, the elevated protein catabolism is difficult to abolish, even during aggressive nutrition support. Thus, in patients with prolonged aggression, these alterations produce a progressive loss of body cell mass and foster the development of malnutrition and it dire complications. In this review, the relevant physiologic data and the nutritional implications related to energy metabolism in septic and injured patients are discussed, while potential therapeutic strategies are proposed.

  16. Late-onset neonatal sepsis: recent developments.

    PubMed

    Dong, Ying; Speer, Christian P

    2015-05-01

    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.

  17. Automated lower limb prosthesis design

    NASA Astrophysics Data System (ADS)

    Bhatia, Gulab H.; Commean, Paul K.; Smith, Kirk E.; Vannier, Michael W.

    1994-09-01

    The design of lower limb prostheses requires definitive geometric data to customize socket shape. Optical surface imaging and spiral x-ray computed tomography were applied to geometric analysis of limb residua in below knee (BK) amputees. Residua (limb remnants after amputation) of BK amputees were digitized and measured. Surface (optical) and volumetric (CT) data of the residuum were used to generate solid models and specify socket shape in (SDRC I-DEAS) CAD software. Volume measurements on the solid models were found to correspond within 2% of surface models and direct determinations made using Archimedean weighing. Anatomic 3D reconstruction of the residuum by optical surface and spiral x-ray computed tomography imaging are feasible modalities for prosthesis design.

  18. 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.

  19. Improving the care of sepsis: Between system redesign and professional responsibility: A roundtable discussion in the world sepsis day, September 25, 2013, Riyadh, Saudi Arabia.

    PubMed

    Arabi, Yaseen; Alamry, Ahmed; Levy, Mitchell M; Taher, Saadi; Marini, Abdellatif M

    2014-07-01

    This paper summarizes the roundtable discussion in September 25, 2013, Riyadh, Saudi Arabia as part of the World Sepsis Day held in King Abdulaziz Medical City, Riyadh. The objectives of the roundtable discussion were to (1) review the chasm between the current management of sepsis and best practice, (2) discuss system redesign and role of the microsystem in sepsis management, (3) emphasize the multidisciplinary nature of the care of sepsis and that improvement of the care of sepsis is the responsibility of all, (4) discuss the bundle concept in sepsis management, and (5) reflect on the individual responsibility of the health care team toward sepsis with a focus on accountability and the moral agent.

  20. 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. PMID:27630891

  1. Trends and disparities in sepsis hospitalisations in Victoria, Australia.

    PubMed

    Ore, Timothy

    2015-12-14

    Objective The aim of the present study was to determine the clinical and epidemiological characteristics of patients with sepsis admitted to hospitals in Victoria, Australia, during the period 2004-14. The data include incidence, severity and mortality.Methods In all, 44 222 sepsis hospitalisations were identified between 2004-05 and 2013-14 from the Victorian Admitted Episodes Dataset. The dataset contains clinical and demographic information on all admissions to acute public and private hospitals. Using the International Classification of Diseases (10th Revision) Australian Modification codes, incidence rates, severity of disease and mortality were calculated.Results Sepsis hospitalisation rates per 10 000 population increased significantly (P < 0.01) over the period, from 6.9 (95% confidence interval (CI) 5.6-7.8) to 10.0 (95% CI 9.1-11.1), an annual growth rate of 3.8%. The age-standardised in-hospital death rates per 100 000 population grew significantly (P < 0.01) from 9.2 (95% CI 7.8-10.4) in 2004-05 to 13.0 (95% CI 11.7-14.6) in 2013-14, an annual growth rate of 3.1%. Among people under 45 years of age, the 0-4 years age group had the highest hospitalisation rate (3.0 per 10 000 population; 95% CI 2.7-3.4). Nearly half (46.2%) of all sepsis hospitalisations were among patients born overseas, with a rate of 14.5 per 10 000 population (95% CI 12.4-16.2) in that group compared with a rate of 5.9 per 10 000 population (95% CI 5.3-6.7) for patients born in Australia. The age-standardised sepsis hospitalisation rate was 2.6-fold greater in the lowest compared with highest socioeconomic areas (12.7 per 10 000 population (95% CI 11.2-13.8) vs 4.8 per 10 000 population (95% CI 4.1-5.7), respectively).Conclusion This paper shows a significant upward trend in both sepsis separation rates and in-hospital death rates over the period; unlike sepsis, in-hospital death rates from all diagnoses fell over the same period. The results can be used to stimulate review of

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

    PubMed

    Lee, Soon Min; Chang, Meayoung; Kim, Ki-Soo

    2015-10-01

    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.

  3. Maresin 1 Mitigates Inflammatory Response and Protects Mice from Sepsis

    PubMed Central

    Li, Ruidong; Wang, Yaxin; Ma, Zhijun; Ma, Muyuan; Wang, Di; Xie, Gengchen; Yin, Yuping

    2016-01-01

    Sepsis, frequently caused by infection of bacteria, is considered as an uncontrollable systematic inflammation response syndrome (SIRS). Maresin 1 (Mar1) is a new proresolving mediator with potent anti-inflammatory effect in several animal models. However, its effect in sepsis is still not investigated. To address this question, we developed sepsis model in BALB/c mice by cecal ligation and puncture (CLP) with or without Mar1 treatment. Our data showed that Mar1 markedly improved survival rate and decreased the levels of proinflammatory cytokines in CLP mice such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Furthermore, Mar1 reduced serum level of lipopolysaccharide (LPS) and enhanced the bacteria clearance in mice sepsis model. Moreover, Mar1 attenuated lung injury and decreased level of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cre), and blood urea nitrogen (BUN) in serum in mice after CLP surgery. Treatment with Mar1 inhibited activation of nuclear factor kappa B (NF-κb) pathway. In conclusion, Mar1 exhibited protective effect in sepsis by reducing LPS, bacteria burden in serum, inhibiting inflammation response, and improving vital organ function. The possible mechanism is partly involved in inhibition of NF-κb activation. PMID:28042205

  4. Role of Pore-Forming Toxins in Neonatal Sepsis

    PubMed Central

    Sonnen, Andreas F.-P.

    2013-01-01

    Protein toxins are important virulence factors contributing to neonatal sepsis. The major pathogens of neonatal sepsis, group B Streptococci, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus, secrete toxins of different molecular nature, which are key for defining the disease. Amongst these toxins are pore-forming exotoxins that are expressed as soluble monomers prior to engagement of the target cell membrane with subsequent formation of an aqueous membrane pore. Membrane pore formation is not only a means for immediate lysis of the targeted cell but also a general mechanism that contributes to penetration of epithelial barriers and evasion of the immune system, thus creating survival niches for the pathogens. Pore-forming toxins, however, can also contribute to the induction of inflammation and hence to the manifestation of sepsis. Clearly, pore-forming toxins are not the sole factors that drive sepsis progression, but they often act in concert with other bacterial effectors, especially in the initial stages of neonatal sepsis manifestation. PMID:23710203

  5. Endocrine dysfunction in sepsis: a beneficial or deleterious host response?

    PubMed

    Gheorghiţă, Valeriu; Barbu, Alina Elena; Gheorghiu, Monica Livia; Căruntu, Florin Alexandru

    2015-03-01

    Sepsis is a systemic, deleterious inflammatory host response triggered by an infective agent leading to severe sepsis, septic shock and multi-organ failure. The host response to infection involves a complex, organized and coherent interaction between immune, autonomic, neuroendocrine and behavioral systems. Recent data have confirmed that disturbances of the autonomic nervous and neuroendocrine systems could contribute to sepsis-induced organ dysfunction. Through this review, we aimed to summarize the current knowledge about the endocrine dysfunction as response to sepsis, specifically addressed to vasopressin, copeptin, cortisol, insulin and leptin. We searched the following readily accessible, clinically relevant databases: PubMed, UpToDate, BioMed Central. The immune system could be regarded as a "diffuse sensory organ" that signals the presence of pathogens to the brain through different pathways, such as the vagus nerve, endothelial activation/dysfunction, cytokines and neurotoxic mediators and the circumventricular organs, especially the neurohypophysis. The hormonal profile changes substantially as a consequence of inflammatory mediators and microorganism products leading to inappropriately low levels of vasopressin, sick euthyroid syndrome, reduced adrenal responsiveness to ACTH, insulin resistance, hyperglycemia as well as hyperleptinemia. In conclusion, clinical diagnosis of this "pan-endocrine illness" is frequently challenging due to the many limiting factors. The most important benefits of endocrine markers in the management of sepsis may be reflected by their potential to be used as biomarkers in different scoring systems to estimate the severity of the disease and the risk of death.

  6. Immunological Defects in Neonatal Sepsis and Potential Therapeutic Approaches

    PubMed Central

    Raymond, Steven L.; Stortz, Julie A.; Mira, Juan C.; Larson, Shawn D.; Wynn, James L.; Moldawer, Lyle L.

    2017-01-01

    Despite advances in critical care medicine, neonatal sepsis remains a major cause of morbidity and mortality worldwide, with the greatest risk affecting very low birth weight, preterm neonates. The presentation of neonatal sepsis varies markedly from its presentation in adults, and there is no clear consensus definition of neonatal sepsis. Previous work has demonstrated that when neonates become septic, death can occur rapidly over a matter of hours or days and is generally associated with inflammation, organ injury, and respiratory failure. Studies of the transcriptomic response by neonates to infection and sepsis have led to unique insights into the early proinflammatory and host protective responses to sepsis. Paradoxically, this early inflammatory response in neonates, although lethal, is clearly less robust relative to children and adults. Similarly, the expression of genes involved in host protective immunity, particularly neutrophil function, is also markedly deficient. As a result, neonates have both a diminished inflammatory and protective immune response to infection which may explain their increased risk to infection, and their reduced ability to clear infections. Such studies imply that novel approaches unique to the neonate will be required for the development of both diagnostics and therapeutics in this high at-risk population. PMID:28224121

  7. [Usefulness of Procalcitonin Measurement for the Detection of Sepsis].

    PubMed

    Toh, Hiromi; Harada, Sadako; Kakudou, Tomoko; Era, Fumiyoshi; Tokushige, Chiemi; Yoshimura, Hisae; Kawashima, Hironobu; Ohkubo, Kumiko; Ishikura, Hiroyasu; Matsunaga, Akira

    2014-10-01

    Procalcitonin (PCT) is a frequently used marker for bacterial sepsis. The present study was aimed to assess the usefulness of PCT measurement in patient with sepsis. We studied the relationship between serum PCT level and blood culture in clinical 209 cases admitted from January 2010 through June 2010. We compared PCT level with blood culture results and other clinical data, and diagnosis such as sepsis and systemic inflammatory response syndrome (SIRS) were obtained from the medical records. In the case of patients with positive blood cultures and PCT < 0.5 ng/mL, the false- positive blood culture was suspected. The possibility of bacteremia was high when PCT level was more than 0.5 ng/mL. Patients with PCT ≥ 2 ng/mL had significant correlation with the presence of sepsis. The PCT measurement could be performed and reported rapidly and provided valuable information before availability of culture results. In this study, we found that the PCT would be a useful biomarker for confirming and ruling out sepsis.

  8. Use of miRNAs as Biomarkers in Sepsis

    PubMed Central

    Dumache, Raluca; Rogobete, Alexandru Florin; Bedreag, Ovidiu Horea; Sarandan, Mirela; Cradigati, Alina Carmen; Papurica, Marius; Dumbuleu, Corina Maria; Nartita, Radu; Sandesc, Dorel

    2015-01-01

    Sepsis is one of the most common causes of death in critical patients. Severe generalized inflammation, infections, and severe physiological imbalances significantly decrease the survival rate with more than 50%. Moreover, monitoring, evaluation, and therapy management often become extremely difficult for the clinician in this type of patients. Current methods of diagnosing sepsis vary based especially on the determination of biochemical-humoral markers, such as cytokines, components of the complement, and proinflammatory and anti-inflammatory compounds. Recent studies highlight the use of new biomarkers for sepsis, namely, miRNAs. miRNAs belong to a class of small, noncoding RNAs with an approximate content of 19–23 nucleotides. Following biochemical and physiological imbalances, the expression of miRNAs in blood or other body fluids changes significantly. Moreover, its stability, specificity, and selectivity make miRNAs ideal candidates for sepsis biomarkers. In conclusion, we can affirm that stable species of circulating miRNAs represent potential biomarkers for monitoring the evolution of sepsis. PMID:26221578

  9. Gram-negative sepsis: a dilemma of modern medicine.

    PubMed Central

    Bone, R C

    1993-01-01

    Gram-negative sepsis is an increasingly common problem, with up to 300,000 cases occurring each year in the United States alone. Despite the ongoing development of new antibiotics, mortality from gram-negative sepsis remains unacceptably high. To stimulate earlier therapeutic intervention by physicians, a new set of broad definitions has been proposed to define the systemic inflammatory response characteristic of sepsis. In this review, the signs and symptoms of this progressive, injurious process are reviewed and its management is discussed, as are the mechanisms by which bacterial endotoxin triggers the biochemical events that lead to such serious complications as shock, adult respiratory distress syndrome, and disseminated intravascular coagulation. These events often occur even when appropriate antimicrobial therapy has been instituted. An increased understanding of the structure of endotoxin and its role in the development of sepsis, together with advances in hybridoma technology, has led to the development of monoclonal antibodies that bind to endotoxin and significantly attenuate its adverse effects. These agents promise to substantially reduce the morbidity and mortality associated with gram-negative sepsis. PMID:8457980

  10. Sepsis and ARDS: The Dark Side of Histones.

    PubMed

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

    2015-01-01

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

  11. Crosstalk between inflammation and coagulation: the lessons of sepsis.

    PubMed

    van der Poll, Tom; Levi, Marcel

    2012-09-01

    Sepsis results in the concurrent activation of inflammatory and procoagulant pathways. Bacterial products and proinflammatory cytokines trigger the coagulation system primarily via induction of tissue factor. During sepsis, activation of coagulation is accompanied by impaired function of major anticoagulant mechanisms, including antithrombin, the protein C system and fibrinolysis. Protease activated receptors (PARs) form the molecular connection between coagulation and inflammation, and especially PAR1 seems to play an eminent role in sepsis pathogenesis. Activated protein C (APC) can cleave PAR1 when associated with either the endothelial protein C receptor (EPCR) or CD11b/CD18, resulting in broad cytoprotective effects mediated by sphingosine 1 phosphate (S1P) receptor 1 (S1P1). In contrast, activation of PAR1 by high dose thrombin results in barrier disruptive effects in endothelial cells via an S1P3 dependent mechanism. Recombinant APC protects against mortality in experimental endotoxemia and sepsis by effects that can be mediated by either EPCR - PAR1 dependent (endothelial cells, dendritic cells) or CD11b/CD18 - PAR1 dependent (macrophages) mechanisms. These protective APC effects do not rely on the anticoagulant properties of this protein. APC mutants that lack anticoagulant properties but retain the capacity to activate PAR1 are promising new drugs for sepsis treatment.

  12. Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding

    PubMed Central

    Iskander, Kendra N.; Osuchowski, Marcin F.; Stearns-Kurosawa, Deborah J.; Kurosawa, Shinichiro; Stepien, David; Valentine, Catherine

    2013-01-01

    Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed. PMID:23899564

  13. Fingernails Yield Clues to Limb Regeneration

    MedlinePlus

    ... embryonic development, as well as limb regeneration in amphibians. They found that the Wnt pathway was active ... nerve cells was crucial for limb regeneration in amphibians, so they wanted to examine their role in ...

  14. 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…

  15. Triple Compliant Limbs with Adaptive Body Structure

    DTIC Science & Technology

    2012-06-20

    legs, with the third limb being used as a tail to add stability and/or manipulation • One or Two Legged Hop : One or two limbs are used to store and...release energy to hop while the third limb is used for either stability or manipulation tasks • Brachiating: Limbs are used to grab objects overhead...2 LEG HOP (Energy Release) BRACHIATING DISMOUNTING (IMPACT ABSORBTION) CARTWHEELING 5 Gaits & Transitions Variety of gaits can be realized using

  16. The accessory limb model: an alternative experimental system of limb regeneration.

    PubMed

    Endo, Tetsuya; Gardiner, David M; Makanae, Aki; Satoh, Akira

    2015-01-01

    Accessory limb model (ALM) was developed as an experimental model and functional assay for limb regeneration. The ALM provides several ways to identify pathways and test for signaling molecules that regulate limb regeneration. Here, we summarize the history of the ALM and describe the specific details involved in inducing ectopic blastemas and limbs from a skin wound on the side of the arm.

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

    PubMed Central

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

    2017-01-01

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

  18. Severe sepsis and septic shock: clinical overview and update on management.

    PubMed

    Cawcutt, Kelly A; Peters, Steve G

    2014-11-01

    Sepsis is among the oldest themes in medicine; however, despite modern advances, it remains a leading cause of death in the United States. Every clinician should be able to recognize the signs and symptoms of sepsis, along with early management strategies, to expeditiously provide appropriate care and decrease resultant morbidity and mortality. This review addresses the definitions, pathogenesis, clinical manifestations, management, and outcomes of patients with sepsis, severe sepsis, and septic shock.

  19. 981: Evaluation of Burn Sepsis Automated Alerts in an Intensive Care Unit

    DTIC Science & Technology

    2014-12-01

    DEC 2014 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE 981:Evaluation of Burn Sepsis Automated Alerts in an Intensive Care...BURN SEPSIS AUTOMATED ALERTS IN AN INTENSIVE CARE UNIT Elizabeth Mann-Salinas1, Nicole Caldwell1, Maria Serio-Melvin1, David Luellen1, Kevin Chung1...the burn unit initiated Sepsis Alert soft- ware. Continuous electronic medical record (EMR) screening used novel predic- tors of burn sepsis (Burn6

  20. The coagulopathy in sepsis: significance and implications for treatment

    PubMed Central

    Saracco, Paola; Vitale, Pasquale; Scolfaro, Carlo; Pollio, Berardino; Pagliarino, Mauro; Timeus, Fabio

    2011-01-01

    Sepsis related coagulopathy ranges from mild laboratory alterations up to severe disseminated intravascular coagulation (DIC). There is evidence that DIC is involved in the pathogenesis of microvascular dysfunction contributing to organ failure. Additionally, the systemic activation of coagulation, by consuming platelets and coagulation factors, may cause bleeding. Thrombin generation via the tissue factor/factor VIIa route, contemporary depression of antithrombin and protein C anticoagulant systems, as well as impaired fibrin degradation, due to high circulating levels of PAI-1, contribute to enhanced intravascular fibrin deposition. This deranged coagulopathy is an independent predictor of clinical outcome in patients with severe sepsis. Innovative supportive strategies aiming at the inhibition of coagulation activation should comprise inhibition of tissue factor-mediated activation or restoration of physiological anticoagulant pathways, as the administration of recombinant human activated protein C or concentrate. In spite of some promising initial studies, additional trials are needed to define their clinical effectiveness in adults and children with severe sepsis. PMID:22355515

  1. The future of murine sepsis and trauma research models

    PubMed Central

    Efron, Philip A.; Mohr, Alicia M.; Moore, Frederick A.; Moldawer, Lyle L.

    2015-01-01

    Recent comparisons of the murine and human transcriptome in health and disease have called into question the appropriateness of the use of murine models for human sepsis and trauma research. More specifically, researchers have debated the suitability of mouse models of severe inflammation that is intended for eventual translation to human patients. This mini-review outlines this recent research, as well as specifically defines the arguments for and against murine models of sepsis and trauma research based on these transcriptional studies. In addition, we review newer advancements in murine models of infection and injury and define what we envision as an evolving but viable future for murine studies of sepsis and trauma. PMID:26034205

  2. Sepsis requiring intensive care following intramuscular injections: two case reports

    PubMed Central

    Velissaris, Dimitrios; Matzaroglou, Charis; Kalogeropoulou, Christina; Karamouzos, Vassilios; Filos, Kriton

    2009-01-01

    Introduction Intramuscular injections can rarely result in serious infectious complications such as abscesses which may progress to bacteraemia and generalized sepsis. These complications are rare, but can be life threatening, as they can lead to multi-organ failure associated with high morbidity and mortality. Case presentation In this report we present two patients who developed life-threatening infections after intramuscular injections. They were admitted to the hospital, had prompt surgical drainage, required ICU admission for severe sepsis, were treated with an early goal-directed therapy protocol and had a good outcome. Conclusion Sepsis is a rare, potentially life-threatening complication after intramuscular injections. Timely surgical drainage followed by appropriate ICU care and early goal directed therapy is crucial and may contribute to a good outcome in these rare cases. PMID:19918523

  3. A novel role for matrix metalloproteinase-8 in sepsis

    PubMed Central

    Solan, Patrick D.; Dunsmore, Katherine E.; Denenberg, Alvin G.; Odoms, Kelli; Zingarelli, Basilia; Wong, Hector R.

    2011-01-01

    Objectives Matrix metalloproteinase-8 (MMP-8) mRNA expression was previously found to be increased in whole blood of children with septic shock. The impact of this finding on the severity and inflammatory response to sepsis is unknown. Here, we investigate the relationship between MMP-8 and disease severity in a children with septic shock. We further corroborate the role of MMP-8 in sepsis in a murine model. Design Retrospective observational clinical study and randomized controlled laboratory experiments. Setting Pediatric intensive care units and an animal research facility at an academic children’s hospital. Patients/Subjects Patients age ≤ 10 years admitted to the intensive care unit with a diagnosis of septic shock. For laboratory studies, we utilized male mice deficient for MMP-8 and male wild type C57/Bl6 mice. Interventions Blood from children with septic shock was analyzed for MMP-8 mRNA expression and MMP-8 activity, and correlated with disease severity based on mortality and degree of organ failure. A murine model of sepsis was used to explore the effect of genetic and pharmacologic inhibition of MMP-8 on the inflammatory response to sepsis. Finally, activation of nuclear factor-κB (NF-κB) was assessed both in vitro and in vivo. Measurements and Main Results Increased MMP-8 mRNA expression and activity in septic shock correlates with decreased survival and increased organ failure in pediatric patients. Genetic and pharmacologic inhibition of MMP-8 leads to improved survival and a blunted inflammatory profile in a murine model of sepsis. We also identify MMP-8 as a direct in vitro activator of the pro-inflammatory transcription factor, NF-κB. Conclusions MMP-8 is a novel modulator of inflammation during sepsis and a potential therapeutic target. PMID:22020238

  4. Toxin Mediates Sepsis Caused by Methicillin-Resistant Staphylococcus epidermidis

    PubMed Central

    Qin, Li; Da, Fei; Tan, Daniel C. S.; Nguyen, Thuan H.; Fu, Chih-Lung; Tan, Vee Y.; Sturdevant, Daniel E.

    2017-01-01

    Bacterial sepsis is a major killer in hospitalized patients. Coagulase-negative staphylococci (CNS) with the leading species Staphylococcus epidermidis are the most frequent causes of nosocomial sepsis, with most infectious isolates being methicillin-resistant. However, which bacterial factors underlie the pathogenesis of CNS sepsis is unknown. While it has been commonly believed that invariant structures on the surface of CNS trigger sepsis by causing an over-reaction of the immune system, we show here that sepsis caused by methicillin-resistant S. epidermidis is to a large extent mediated by the methicillin resistance island-encoded peptide toxin, PSM-mec. PSM-mec contributed to bacterial survival in whole human blood and resistance to neutrophil-mediated killing, and caused significantly increased mortality and cytokine expression in a mouse sepsis model. Furthermore, we show that the PSM-mec peptide itself, rather than the regulatory RNA in which its gene is embedded, is responsible for the observed virulence phenotype. This finding is of particular importance given the contrasting roles of the psm-mec locus that have been reported in S. aureus strains, inasmuch as our findings suggest that the psm-mec locus may exert effects in the background of S. aureus strains that differ from its original role in the CNS environment due to originally “unintended” interferences. Notably, while toxins have never been clearly implied in CNS infections, our tissue culture and mouse infection model data indicate that an important type of infection caused by the predominant CNS species is mediated to a large extent by a toxin. These findings suggest that CNS infections may be amenable to virulence-targeted drug development approaches. PMID:28151994

  5. Optical detection of sepsis markers using liquid crystal based biosensors

    NASA Astrophysics Data System (ADS)

    McCamley, Maureen K.; Artenstein, Andrew W.; Opal, Steven M.; Crawford, Gregory P.

    2007-02-01

    A liquid crystal based biosensor for the detection and diagnosis of sepsis is currently in development. Sepsis, a major clinical syndrome with a significant public health burden in the US due to a large elderly population, is the systemic response of the body to a localized infection and is defined as the combination of pathologic infection and physiological changes. Bacterial infections are responsible for 90% of cases of sepsis in the US. Currently there is no bedside diagnostic available to positively identify sepsis. The basic detection scheme employed in a liquid crystal biosensor contains attributes that would find value in a clinical setting, especially for the early detection of sepsis. Utilizing the unique properties of liquid crystals, such as birefringence, a bedside diagnostic is in development which will optically report the presence of biomolecules. In a septic patient, an endotoxin known as lipopolysaccharide (LPS) is released from the outer membrane of Gram-negative bacteria and can be found in the blood stream. It is hypothesized that this long chained molecule will cause local disruptions to the open surface of a sensor containing aligned liquid crystal. The bulk liquid crystal ampli.es these local changes at the surface due to the presence of the sepsis marker, providing an optical readout through polarizing microscopy images. Liquid crystal sensors consisting of both square and circular grids, 100-200 μm in size, have been fabricated and filled with a common liquid crystal material, 5CB. Homeotropic alignment was confirmed using polarizing microscopy. The grids were then contacted with either saline only (control), or saline with varying concentrations of LPS. Changes in the con.guration of the nematic director of the liquid crystal were observed through the range of concentrations tested (5mg/mL - 1pg/mL) which have been confirmed by a consulting physician as clinically relevant levels.

  6. Fatal sepsis caused by an unusual Klebsiella species that was misidentified by an automated identification system.

    PubMed

    Seki, Masafumi; Gotoh, Kazuyoshi; Nakamura, Shota; Akeda, Yukihiro; Yoshii, Tadashi; Miyaguchi, Shinichi; Inohara, Hidenori; Horii, Toshihiro; Oishi, Kazunori; Iida, Tetsuya; Tomono, Kazunori

    2013-05-01

    This is a description of fatal sepsis caused by infection with Klebsiella variicola, which is an isolate genetically related to Klebsiella pneumoniae. The patient's condition was incorrectly diagnosed as common sepsis caused by K. pneumoniae, which was identified using an automated identification system, but next-generation sequencing and the non-fermentation of adonitol finally identified the cause of sepsis as K. variicola.

  7. Role of Toll-like receptors in the development of sepsis.

    PubMed

    Tsujimoto, Hironori; Ono, Satoshi; Efron, Philip A; Scumpia, Philip O; Moldawer, Lyle L; Mochizuki, Hidetaka

    2008-03-01

    The outcome of sepsis and septic shock has not significantly improved in recent decades despite the development of numerous drugs and supportive care therapies. To reduce sepsis-related mortality, a better understanding of molecular mechanism(s) associated with the development of sepsis and sepsis-related organ injury is essential. There is increasing evidence that Toll-like receptors (TLRs) play a key role in the mediation of systemic responses to invading pathogens during sepsis. However, the role of TLRs in the development of sepsis and in sepsis-related organ injury remains debatable. In this review, we focus on the biological significance of TLRs during sepsis. Medline was searched for pertinent publications relating to TLRs, with emphasis on their clinical and pathophysiological importance in sepsis. In addition, a summary of the authors' own experimental data from this field was set in the context of current knowledge regarding TLRs. In both animal models and human sepsis, TLRs are highly expressed on monocytes/macrophages, and this TLR expression may not simply be a ligand-specific response in such an environment. The fact that TLR signaling enables TLRs to recognize harmful mediators induced by invading pathogens may be associated with a positive feedback loop for the inflammatory response among different cell populations. This mechanism(s) may contribute to the organ dysfunction and mortality that occurs in sepsis. A better understanding of TLR biology may unveil novel therapeutic approaches for sepsis.

  8. Neuroanatomy and Physiology of Brain Dysfunction in Sepsis.

    PubMed

    Mazeraud, Aurelien; Pascal, Quentin; Verdonk, Franck; Heming, Nicholas; Chrétien, Fabrice; Sharshar, Tarek

    2016-06-01

    Sepsis-associated encephalopathy (SAE), a complication of sepsis, is often complicated by acute and long-term brain dysfunction. SAE is associated with electroencephalogram pattern changes and abnormal neuroimaging findings. The major processes involved are neuroinflammation, circulatory dysfunction, and excitotoxicity. Neuroinflammation and microcirculatory alterations are diffuse, whereas excitotoxicity might occur in more specific structures involved in the response to stress and the control of vital functions. A dysfunction of the brainstem, amygdala, and hippocampus might account for the increased mortality, psychological disorders, and cognitive impairment. This review summarizes clinical and paraclinical features of SAE and describes its mechanisms at cellular and structural levels.

  9. Sepsis, severe sepsis, and septic shock: current evidence for emergency department management.

    PubMed

    Booker, Ethan

    2011-05-01

    In the middle of a busy shift, a patient arrives by ambulance from a local long-term care facility with a report of altered mental status. You enter the room to find a chronically ill-appearing 85-year-old man with fever, tachycardia, and hypotension, and it is instantly apparent that this patient is septic. What is not clear is what the source is, what modifications in treatment might be necessary based on preexisting microbial resistance, and which of the array of invasive resuscitation techniques are appropriate when meaningful recovery is questionable and efforts may not be desired by the patient and family. You order IV fluids and broad-spectrum antibiotics; send lab tests, including lactate and cultures of blood, urine, and sputum; and begin to review his extensive history to discuss goals of care with his family and primary doctor. While reviewing these issues, a 54-year-old woman with a history of asthma is brought straight back from triage with respiratory distress. You listen to her lungs, expecting wheezes, but hear decreased lung sounds at the right base, preserved air movement elsewhere, and her skin radiates heat. Now, on the monitor, she has a heart rate of 135 beats per minute, blood pressure of 90/60 mm Hg, O2 saturation of 86%, and a temperature of 39.4 degrees C (103 degrees F). You again identify sepsis and instruct your team that you will be using your department's severe sepsis protocol. Equipment for monitoring and procedures is assembled, your staff provides preprinted order and monitoring flow sheets, and the ICU is alerted. Within an hour, the patient is intubated, has a central line placed, and has received IV fluids, broad-spectrum antibiotics and norepinephrine, and you are pleased to see a MAP of 67 mm Hg, a lactate decreasing from an initial value of 7.0, CVP of 10, and ScvO2 of 78%.

  10. Community-, Healthcare- and Hospital-Acquired Severe Sepsis Hospitalizations in the University HealthSystem Consortium

    PubMed Central

    Page, David B.; Donnelly, John P.; Wang, Henry E.

    2015-01-01

    Objectives Severe sepsis poses a major burden on the U.S. healthcare system. Previous epidemiologic studies have not differentiated community-acquired severe sepsis from healthcare-associated severe sepsis or hospital-acquired severe sepsis hospitalizations. We sought to compare and contrast community-acquired severe sepsis, healthcare-associated severe sepsis, and hospital-acquired severe sepsis hospitalizations in a national hospital sample. Setting United States Interventions None Measurements & Main Results Prevalence of community-acquired severe sepsis, healthcare-associated severe sepsis, and hospital-acquired severe sepsis, adjusted hospital mortality, length of hospitalization, length of stay in an ICU, and hospital costs. Among 3,355,753 hospital discharges, there were 307,491 with severe sepsis, including 193,081 (62.8%) community-acquired severe sepsis, 79,581 (25.9%) healthcare-associated severe sepsis, and 34,829 (11.3%) hospital-acquired severe sepsis. Hospital-acquired severe sepsis and healthcare-associated severe sepsis exhibited higher in-hospital mortality than community-acquired severe sepsis (hospital-acquired [19.2%] vs healthcare-associated [12.8%] vs community-acquired [8.6%]). Hospital-acquired severe sepsis had greater resource utilization than both healthcare-associated severe sepsis and community-acquired severe sepsis, with higher median length of hospital stay (hospital acquired [17 d] vs healthcare associated [7 d] vs community-acquired [6 d]), median length of ICU stay (hospital-acquired [8 d] vs healthcare-associated [3 d] vs community-acquired [3 d]), and median hospital costs (hospital-acquired [$38,369] vs healthcare-associated [$8,796] vs community-acquired [$7,024]). Conclusions In this series, severe sepsis hospitalizations included CA-SS (62.8%), HCA-SS (25.9%) and HA-SS (11.3%) cases. HA-SS was associated with both higher mortality and resource utilization than CA-SS and HCA-SS. PMID:26110490

  11. Continuum limbed robots for locomotion

    NASA Astrophysics Data System (ADS)

    Mutlu, Alper

    This thesis focuses on continuum robots based on pneumatic muscle technology. We introduce a novel approach to use these muscles as limbs of lightweight legged robots. The flexibility of the continuum legs of these robots offers the potential to perform some duties that are not possible with classical rigid-link robots. Potential applications are as space robots in low gravity, and as cave explorer robots. The thesis covers the fabrication process of continuum pneumatic muscles and limbs. It also provides some new experimental data on this technology. Afterwards, the designs of two different novel continuum robots - one tripod, one quadruped - are introduced. Experimental data from tests using the robots is provided. The experimental results are the first published example of locomotion with tripod and quadruped continuum legged robots. Finally, discussion of the results and how far this technology can go forward is presented.

  12. Therapeutic interventions in sepsis: current and anticipated pharmacological agents

    PubMed Central

    Shukla, Prashant; Rao, G Madhava; Pandey, Gitu; Sharma, Shweta; Mittapelly, Naresh; Shegokar, Ranjita; Mishra, Prabhat Ranjan

    2014-01-01

    Sepsis is a clinical syndrome characterized by a multisystem response to a pathogenic assault due to underlying infection that involves a combination of interconnected biochemical, cellular and organ–organ interactive networks. After the withdrawal of recombinant human-activated protein C (rAPC), researchers and physicians have continued to search for new therapeutic approaches and targets against sepsis, effective in both hypo- and hyperinflammatory states. Currently, statins are being evaluated as a viable option in clinical trials. Many agents that have shown favourable results in experimental sepsis are not clinically effective or have not been clinically evaluated. Apart from developing new therapeutic molecules, there is great scope for for developing a variety of drug delivery strategies, such as nanoparticulate carriers and phospholipid-based systems. These nanoparticulate carriers neutralize intracorporeal LPS as well as deliver therapeutic agents to targeted tissues and subcellular locations. Here, we review and critically discuss the present status and new experimental and clinical approaches for therapeutic intervention in sepsis. PMID:24977655

  13. Fatal sepsis by Bacillus circulans in an immunocompromised patient

    PubMed Central

    Alebouyeh, M; Gooran Orimi, P; Azimi-rad, M; Tajbakhsh, M; Tajeddin, E; Jahani Sherafat, S; Nazemalhosseini mojarad, E; Zali, MR

    2011-01-01

    An immunosuppressed man was admitted to hospital with diarrhea and a history of urinary tract infection. He was subjected to treatment with antibiotics. The patient died of putative severe sepsis. The etiological agent was a carbapenemase producing isolate of Bacillus circulans with resistance to all prescribed antimicrobial agents. PMID:22347600

  14. Gentamicin resistance among Escherichia coli strains isolated in neonatal sepsis.

    PubMed

    Hasvold, J; Bradford, L; Nelson, C; Harrison, C; Attar, M; Stillwell, T

    2013-01-01

    Neonatal sepsis is a significant cause of morbidity and mortality among term and preterm infants. Ampicillin and gentamicin are standard empiric therapy for early onset sepsis. Four cases of neonatal sepsis secondary to Escherichia coli (E. coli) found to be gentamicin resistant occurred within a five week period in one neonatal intensive care unit (NICU). To determine whether these cases could be tied to a single vector of transmission, and to more broadly evaluate the incidence of gentamicin resistant strains of E. coli in the neonatal population at our institution compared to other centers, we reviewed the charts of the four neonates (Infants A through D) and their mothers. The E. coli isolates were sent for Pulse Field Gel Electrophoresis (PFGE) to evaluate for genetic similarity between strains. We also reviewed all positive E. coli cultures from one NICU over a two year period. Infants A and B had genetically indistinguishable strains which matched that of urine and placental cultures of Infant B's mother. Infant C had a genetically distinct organism. Infant D, the identical twin of Infant C, did not have typing performed. Review of all cultures positive for E. coli at our institution showed a 12.9 percent incidence of gentamicin-resistance. A review of other studies showed that rates of resistance vary considerably by institution. We conclude that gentamicin-resistant E. coli is a relatively uncommon cause of neonatal sepsis, but should remain a consideration in patients who deteriorate despite initiation of empiric antibiotics.

  15. Sepsis: Something old, something new, and a systems view.

    PubMed

    Namas, Rami; Zamora, Ruben; Namas, Rajaie; An, Gary; Doyle, John; Dick, Thomas E; Jacono, Frank J; Androulakis, Ioannis P; Nieman, Gary F; Chang, Steve; Billiar, Timothy R; Kellum, John A; Angus, Derek C; Vodovotz, Yoram

    2012-06-01

    Sepsis is a clinical syndrome characterized by a multisystem response to a microbial pathogenic insult consisting of a mosaic of interconnected biochemical, cellular, and organ-organ interaction networks. A central thread that connects these responses is inflammation that, while attempting to defend the body and prevent further harm, causes further damage through the feed-forward, proinflammatory effects of damage-associated molecular pattern molecules. In this review, we address the epidemiology and current definitions of sepsis and focus specifically on the biologic cascades that comprise the inflammatory response to sepsis. We suggest that attempts to improve clinical outcomes by targeting specific components of this network have been unsuccessful due to the lack of an integrative, predictive, and individualized systems-based approach to define the time-varying, multidimensional state of the patient. We highlight the translational impact of computational modeling and other complex systems approaches as applied to sepsis, including in silico clinical trials, patient-specific models, and complexity-based assessments of physiology.

  16. Sepsis Patient Detection and Monitor Based on Auto-BN.

    PubMed

    Jiang, Yu; Sha, Lui; Rahmaniheris, Maryam; Wan, Binhua; Hosseini, Mohammad; Tan, Pengliu; Berlin, Richard B

    2016-04-01

    Sepsis is a life-threatening condition caused by an inappropriate immune response to infection, and is a leading cause of elderly death globally. Early recognition of patients and timely antibiotic therapy based on guidelines improve survival rate. Unfortunately, for those patients, it is often detected late because it is too expensive and impractical to perform frequent monitoring for all the elderly. In this paper, we present a risk driven sepsis screening and monitoring framework to shorten the time of onset detection without frequent monitoring of all the elderly. Within this framework, the sepsis ultimate risk of onset probability and mortality is calculated based on a novel temporal probabilistic model named Auto-BN, which consists of time dependent state, state dependent property, and state dependent inference structures. Then, different stages of a patient are encoded into different states, monitoring frequency is encoded into the state dependent property, and screening content is encoded into different state dependent inference structures. In this way, the screening and monitoring frequency and content can be automatically adjusted when encoding the sepsis ultimate risk into the guard of state transition. This allows for flexible manipulation of the tradeoff between screening accuracy and frequency. We evaluate its effectiveness through empirical study, and incorporate it into existing medical guidance system to improve medical healthcare.

  17. Inflammatory Response in Preterm and Very Preterm Newborns with Sepsis

    PubMed Central

    Segura-Cervantes, Enrique; Mancilla-Ramírez, Javier; González-Canudas, Jorge; Alba, Erika; Santillán-Ballesteros, René; Morales-Barquet, Deneb; Sandoval-Plata, Gabriela

    2016-01-01

    The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation. PMID:27293317

  18. Role of extracellular histones in the cardiomyopathy of sepsis.

    PubMed

    Kalbitz, Miriam; Grailer, Jamison J; Fattahi, Fatemeh; Jajou, Lawrence; Herron, Todd J; Campbell, Katherine F; Zetoune, Firas S; Bosmann, Markus; Sarma, J Vidya; Huber-Lang, Markus; Gebhard, Florian; Loaiza, Randall; Valdivia, Hector H; Jalife, José; Russell, Mark W; Ward, Peter A

    2015-05-01

    The purpose of this study was to define the relationship in polymicrobial sepsis (in adult male C57BL/6 mice) between heart dysfunction and the appearance in plasma of extracellular histones. Procedures included induction of sepsis by cecal ligation and puncture and measurement of heart function using echocardiogram/Doppler parameters. We assessed the ability of histones to cause disequilibrium in the redox status and intracellular [Ca(2+)]i levels in cardiomyocytes (CMs) (from mice and rats). We also studied the ability of histones to disturb both functional and electrical responses of hearts perfused with histones. Main findings revealed that extracellular histones appearing in septic plasma required C5a receptors, polymorphonuclear leukocytes (PMNs), and the Nacht-, LRR-, and PYD-domains-containing protein 3 (NLRP3) inflammasome. In vitro exposure of CMs to histones caused loss of homeostasis of the redox system and in [Ca(2+)]i, as well as defects in mitochondrial function. Perfusion of hearts with histones caused electrical and functional dysfunction. Finally, in vivo neutralization of histones in septic mice markedly reduced the parameters of heart dysfunction. Histones caused dysfunction in hearts during polymicrobial sepsis. These events could be attenuated by histone neutralization, suggesting that histones may be targets in the setting of sepsis to reduce cardiac dysfunction.

  19. Soluble Suppression of Tumorigenicity 2 and Echocardiography in Sepsis

    PubMed Central

    Yang, Hyun Suk; Kim, Hanah; Magrini, Laura; Marino, Rossella

    2016-01-01

    Soluble suppression of tumorigenicity 2 (sST2) has emerged as a biomarker of cardiac stretch or remodeling, and has demonstrated a role in acutely decompensated heart failure. However, its role in sepsis-induced cardiac dysfunction is still unknown. We explored whether sST2 serum concentration reflects either systolic or diastolic dysfunction as measured by Doppler echocardiography. In a total of 127 patients with sepsis, correlations between sST2 and blood pressure, left ventricular (LV) ejection fraction, LV diastolic filling (ratio of early transmitral flow velocity to early diastolic mitral annulus velocity), and resting pulmonary arterial pressure were evaluated. Correlations between sST2 and other sepsis biomarkers (high-sensitivity C-reactive protein [hs-CRP] and procalcitonin) were also examined. sST2 showed a moderate correlation with mean arterial pressure (r=-0.3499) but no correlation with LV ejection fraction, diastolic filling, or resting pulmonary hypertension. It showed moderate correlations with hs-CRP and procalcitonin (r=0.2608 and r=0.3829, respectively). sST2 might have a role as a biomarker of shock or inflammation, but it cannot reflect echocardiographic findings of LV ejection fraction or diastolic filling in sepsis. PMID:27578513

  20. Clinical Decision Support for Early Recognition of Sepsis

    PubMed Central

    Amland, Robert C.; Hahn-Cover, Kristin E.

    2014-01-01

    Sepsis is an inflammatory response triggered by infection, with a high in-hospital mortality rate. Early recognition and treatment can reverse the inflammatory response, with evidence of improved patient outcomes. One challenge clinicians face is identifying the inflammatory syndrome against the background of the patient’s infectious illness and comorbidities. An approach to this problem is implementation of computerized early warning tools for sepsis. This multicenter retrospective study sought to determine clinimetric performance of a cloud-based computerized sepsis clinical decision support system (CDS), understand the epidemiology of sepsis, and identify opportunities for quality improvement. Data encompassed 6200 adult hospitalizations from 2012 through 2013. Of 13% patients screened-in, 51% were already suspected to have an infection when the system activated. This study focused on a patient cohort screened-in before infection was suspected; median time from arrival to CDS activation was 3.5 hours, and system activation to diagnostic collect was another 8.6 hours. PMID:25385815

  1. A rare nonfatal presentation of disseminated Chromobacterium violaceum sepsis.

    PubMed

    Saboo, Ashwin Rajendra; Vijaykumar, Ramaa; Save, Sushma Uttam; Bavdekar, Sandeep Bhalchandra

    2015-10-01

    We present a case of disseminated Chromobacterium violaceum sepsis with multiple liver and splenic abscesses presenting with skin lesions and cardiogenic shock, and later diagnosed to have chronic granulomatous disease. The patient was treated with prolonged antimicrobial therapy, after which she recovered and remained asymptomatic on follow-up.

  2. Insights into the apoptotic death of immune cells in sepsis.

    PubMed

    Luan, Ying-yi; Yao, Yong-ming; Xiao, Xian-zhong; Sheng, Zhi-yong

    2015-01-01

    Sepsis with subsequent multiple-organ dysfunction is a distinct systemic inflammatory response to concealed or obvious infection, and it is a leading cause of death in intensive care units. Thus, one of the key goals in critical care medicine is to develop novel therapeutic strategies that will affect favorably on outcome of septic patients. In addition to systemic response to infection, apoptosis is implicated to be an important mechanism of the death of immune cells, including neutrophils, macrophages, T lymphocytes, and dendritic cells, and it is usually followed by the development of multiple-organ failure in sepsis. The implication of apoptosis of immune cells is now highlighted by multiple studies that demonstrate that prevention of cell apoptosis can improve survival in relevant animal models of severe sepsis. In this review, we focus on major apoptotic death pathways and molecular mechanisms that regulate apoptosis of different immune cells, and advances in these areas that may be translated into more promising therapies for the prevention and treatment of severe sepsis.

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

    PubMed

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

    2013-01-01

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

  4. Sinomenine hydrochloride protects against polymicrobial sepsis via autophagy.

    PubMed

    Jiang, Yu; Gao, Min; Wang, Wenmei; Lang, Yuejiao; Tong, Zhongyi; Wang, Kangkai; Zhang, Huali; Chen, Guangwen; Liu, Meidong; Yao, Yongming; Xiao, Xianzhong

    2015-01-23

    Sepsis, a systemic inflammatory response to infection, is the major cause of death in intensive care units (ICUs). The mortality rate of sepsis remains high even though the treatment and understanding of sepsis both continue to improve. Sinomenine (SIN) is a natural alkaloid extracted from Chinese medicinal plant Sinomenium acutum, and its hydrochloride salt (Sinomenine hydrochloride, SIN-HCl) is widely used to treat rheumatoid arthritis (RA). However, its role in sepsis remains unclear. In the present study, we investigated the role of SIN-HCl in sepsis induced by cecal ligation and puncture (CLP) in BALB/c mice and the corresponding mechanism. SIN-HCl treatment improved the survival of BALB/c mice that were subjected to CLP and reduced multiple organ dysfunction and the release of systemic inflammatory mediators. Autophagy activities were examined using Western blotting. The results showed that CLP-induced autophagy was elevated, and SIN-HCl treatment further strengthened the autophagy activity. Autophagy blocker 3-methyladenine (3-MA) was used to investigate the mechanism of SIN-HCl in vitro. Autophagy activities were determined by examining the autophagosome formation, which was shown as microtubule-associated protein light chain 3 (LC3) puncta with green immunofluorescence. SIN-HCl reduced lipopolysaccharide (LPS)-induced inflammatory cytokine release and increased autophagy in peritoneal macrophages (PM). 3-MA significantly decreased autophagosome formation induced by LPS and SIN-HCl. The decrease of inflammatory cytokines caused by SIN-HCl was partially aggravated by 3-MA treatment. Taken together, our results indicated that SIN-HCl could improve survival, reduce organ damage, and attenuate the release of inflammatory cytokines induced by CLP, at least in part through regulating autophagy activities.

  5. Sinomenine Hydrochloride Protects against Polymicrobial Sepsis via Autophagy

    PubMed Central

    Jiang, Yu; Gao, Min; Wang, Wenmei; Lang, Yuejiao; Tong, Zhongyi; Wang, Kangkai; Zhang, Huali; Chen, Guangwen; Liu, Meidong; Yao, Yongming; Xiao, Xianzhong

    2015-01-01

    Sepsis, a systemic inflammatory response to infection, is the major cause of death in intensive care units (ICUs). The mortality rate of sepsis remains high even though the treatment and understanding of sepsis both continue to improve. Sinomenine (SIN) is a natural alkaloid extracted from Chinese medicinal plant Sinomenium acutum, and its hydrochloride salt (Sinomenine hydrochloride, SIN-HCl) is widely used to treat rheumatoid arthritis (RA). However, its role in sepsis remains unclear. In the present study, we investigated the role of SIN-HCl in sepsis induced by cecal ligation and puncture (CLP) in BALB/c mice and the corresponding mechanism. SIN-HCl treatment improved the survival of BALB/c mice that were subjected to CLP and reduced multiple organ dysfunction and the release of systemic inflammatory mediators. Autophagy activities were examined using Western blotting. The results showed that CLP-induced autophagy was elevated, and SIN-HCl treatment further strengthened the autophagy activity. Autophagy blocker 3-methyladenine (3-MA) was used to investigate the mechanism of SIN-HCl in vitro. Autophagy activities were determined by examining the autophagosome formation, which was shown as microtubule-associated protein light chain 3 (LC3) puncta with green immunofluorescence. SIN-HCl reduced lipopolysaccharide (LPS)-induced inflammatory cytokine release and increased autophagy in peritoneal macrophages (PM). 3-MA significantly decreased autophagosome formation induced by LPS and SIN-HCl. The decrease of inflammatory cytokines caused by SIN-HCl was partially aggravated by 3-MA treatment. Taken together, our results indicated that SIN-HCl could improve survival, reduce organ damage, and attenuate the release of inflammatory cytokines induced by CLP, at least in part through regulating autophagy activities. PMID:25625512

  6. The heart in sepsis: from basic mechanisms to clinical management.

    PubMed

    Rudiger, Alain; Singer, Mervyn

    2013-03-01

    Septic shock is characterized by circulatory compromise, microcirculatory alterations and mitochondrial damage, which all reduce cellular energy production. In order to reduce the risk of major cell death and a diminished likelihood of recovery, adaptive changes appear to be activated. As a result, cells and organs may survive in a non-functioning hibernation-like condition. Sepsis-induced cardiac dysfunction may represent an example of such functional shutdown. Sepsis-induced myocardial dysfunction is common, corresponds to the severity of sepsis, and is reversible in survivors. Its mechanisms include the attenuation of the adrenergic response at the cardiomyocyte level, alterations of intracellular calcium trafficking and blunted calcium sensitivity of contractile proteins. All these changes are mediated by cytokines. Treatment includes preload optimization with sufficient fluids. However, excessive volume loading is harmful. The first line vasopressor recommended at present is norepinephrine, while vasopressin can be started as a salvage therapy for those not responding to catecholamines. During early sepsis, cardiac output can be increased by dobutamine. While early administration of catecholamines might be necessary to restore adequate organ perfusion, prolonged administration might be harmful. Novel therapies for sepsis-induced cardiac dysfunction are discussed in this article. Cardiac inotropy can be increased by levosimendan, istaroxime or omecamtiv mecarbil without greatly increasing cellular oxygen demands. Heart rate reduction with ivabradine reduces myocardial oxygen expenditure and ameliorates diastolic filling. Beta-blockers additionally reduce local and systemic inflammation. Advances may also come from metabolic interventions such as pyruvate, succinate or high dose insulin substitutions. All these potentially advantageous concepts require rigorous testing before implementation in routine clinical practice.

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

    PubMed Central

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

    2015-01-01

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

  8. Higher platelet reactivity and platelet-monocyte complex formation in Gram-positive sepsis compared to Gram-negative sepsis.

    PubMed

    Tunjungputri, Rahajeng N; van de Heijden, Wouter; Urbanus, Rolf T; de Groot, Philip G; van der Ven, Andre; de Mast, Quirijn

    2016-12-29

    Platelets may play a role in the high risk for vascular complications in Gram-positive sepsis. We compared the platelet reactivity of 15 patients with Gram-positive sepsis, 17 with Gram-negative sepsis and 20 healthy controls using a whole blood flow cytometry-based assay. Patients with Gram-positive sepsis had the highest median fluorescence intensity (MFI) of the platelet membrane expression of P-selectin upon stimulation with high dose adenosine diphosphate (ADP; P = 0.002 vs. Gram-negative and P = 0.005 vs. control groups) and cross-linked collagen-related peptide (CRP-XL; P = 0.02 vs. Gram-negative and P = 0.0001 vs. control groups). The Gram-positive group also demonstrated significantly higher ADP-induced fibrinogen binding (P = 0.001), as wll as platelet-monocyte complex formation (P = 0.02), compared to the Gram-negative group and had the highest plasma levels of platelet factor 4, β-thromboglobulin and soluble P-selectin. In contrast, thrombin-antithrombin complex and C-reactive protein levels were comparable in both patient groups. In conclusion, common Gram-positive pathogens induce platelet hyperreactivity, which may contribute to a higher risk for vascular complications.

  9. Differential expression of toll-like receptor genes: sepsis compared with sterile inflammation 1 day before sepsis diagnosis.

    PubMed

    Lissauer, Matthew E; Johnson, Steven B; Bochicchio, Grant V; Feild, Carinda J; Cross, Alan S; Hasday, Jeffrey D; Whiteford, Craig C; Nussbaumer, William A; Towns, Michael; Scalea, Thomas M

    2009-03-01

    Toll-like receptors (TLRs) are critical components of innate immunity. This study was designed to evaluate differential expression of genes for TLR and associated signal transduction molecules in critically ill patients developing sepsis compared with those with sterile inflammation. Uninfected critically ill patients with systemic inflammatory response syndrome were prospectively followed daily for development of sepsis. They were divided into two groups and compared in a case-control manner: (a) preseptic patients (n = 45) who subsequently developed sepsis, and (b) uninfected systemic inflammatory response syndrome patients (n = 45) who remained uninfected. Whole blood RNA was collected (PAXGene tube) at study entry and 1, 2, and 3 days before clinical sepsis diagnosis (or time-matched uninfected control) and analyzed via Affymetrix Hg_U133 Plus 2.0 microarrays. Genes were considered differentially expressed if they met univariate significance controlled for multiple comparisons at P < 0.005. Differentially expressed probes were uploaded into the Database for Annotation, Visualization and Integrated Discovery. The TLR pathway (Kyoto Encyclopedia of Genes and Genomes-KEGG) significance was determined via Expression Analysis Systematic Explorer (EASE) scoring. A total of 2,974 Affymetrix probes representing 2,190 unique genes were differentially expressed 1 day before sepsis diagnosis. Thirty-six probes representing 25 genes were annotated to the TLR pathway (KEGG) via the Database for Annotation, Visualization and Integrated Discovery with an EASE score at P < 0.0004. Notable TLR genes demonstrating increased expression include TLR-4 (median, 1.43-fold change), TLR-5 (2.08-fold change), and MAPK14 (1.90-fold change). An additional 11 unique genes were manually annotated into the TLR pathway based on known relevance such as TLR-8 (1.54-fold change). The total 36 genes contained 28 showing increased expression and 8 showing decreased expression. Differential gene

  10. Prevalence and characteristics of phantom limb pain and residual limb pain in the long term after upper limb amputation.

    PubMed

    Desmond, Deirdre M; Maclachlan, Malcolm

    2010-09-01

    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 of phantom limb pain during the week preceding assessment was 42.6% (60 of 141). Prevalence of residual limb pain was 43.3% (61 of 141). More than one third of these had some pain constantly or most days. Phantom limb pain was commonly described as 'discomforting' (31 of 60) and associated with 'a little bit' of lifestyle interference (23 of 60). Residual limb pain was most often described as 'discomforting' (27 of 61) or 'distressing' (19 of 61) and was typically associated with low to moderate levels of lifestyle interference. Assessment of multiple dimensions of postamputation pain in the long term after upper limb amputation is warranted.

  11. Disease indicators for sepsis and analysis of sepsis treatment in children using the continuous blood purification technique.

    PubMed

    Liu, J P; Wang, X W; Qie, L P

    2015-05-25

    We analyzed disease severity, inflammation markers, and dynamic changes in cartilage glycoprotein 39 (YKL-40) and C-reactive protein (CRP) levels in children with sepsis before and after treatment with continuous blood purification (CBP). Study participants were 30 children with severe sepsis who were cured from the disease (experimental group) in the Children's Serious Disease Center of In-ner Mongolia People's Hospital between June 2012 and October 2013. Symptomatic CBP treatment was performed after disease severity scoring. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), YKL-40, and CRP levels were tested 0, 12, 24, and 48 h after CBP treatment. YKL-40 mRNA expression in whole blood was determined biochemically, and its expression in peripheral blood was determined with an immunochemical method. We found a significant difference in disease severity scores before and 48 h after CBP treatment (P < 0.05). IL-6, TNF-α, YKL-40, and CRP levels in children with sepsis at 12, 24, and 48 h after CBP treatment significantly differed from those before treatment (P < 0.05). The relative expression of YKL-40 mRNA in the experimental group before CBP treatment significantly increased from that of the control group (P < 0.05). We found a positive correlation between IL-6, TNF-α, YKL-40, and CRP levels 48 h after CBP treatment. In conclusion, CBP is an effective treatment strategy for pediatric sepsis. YKL-40 and CRP can be used to evaluate the effects of sepsis treatment.

  12. Is comorbid status the best predictor of one-year mortality in patients with severe sepsis and sepsis with shock?

    PubMed

    Huddle, N; Arendts, G; Macdonald, S P J; Fatovich, D M; Brown, S G A

    2013-07-01

    Understanding longer term outcomes in critically ill patients will assist treatment decisions, allocation of scarce resources and clinical research in that population. The aim of this study was to compare a well-validated means of determining comorbidity, the Charlson Comorbidity Score, to other verified risk stratification models in predicting one-year mortality and other outcomes in emergency department patients with severe sepsis and sepsis with shock. We conducted a planned subgroup analysis of a prospective observational study, the Critical Illness and Shock Study, in adult patients with sepsis meeting study criteria for critical illness. From emergency department arrival, patients were prospectively enrolled with data collected for a minimum of one year post-enrolment. Scoring systems were derived from this data and compared using receiver-operating characteristic curves. One hundred and four patients were enrolled. The 28-day mortality was 18% and one-year mortality 40%. For predicting one-year mortality, the area under the receiver-operating characteristic curve for age-weighted Charlson Comorbidity Score (0.71, 95% confidence interval 0.61 to 0.81) was at least as good or superior to other scoring systems analysed. The intensive care unit admission rate was 45% and the median hospital length-of-stay was eight days. We conclude that in patients who present to the emergency department with severe sepsis or sepsis with shock, age-weighted Charlson Comorbidity Score is a predictor of one-year mortality that is simple to calculate and at least as accurate as other validated scoring systems.

  13. The molecular regulation of vertebrate limb patterning.

    PubMed

    Butterfield, Natalie C; McGlinn, Edwina; Wicking, Carol

    2010-01-01

    The limb has long been considered a paradigm for organogenesis because of its simplicity and ease of manipulation. However, it has become increasingly clear that the processes required to produce a perfectly formed limb involve complex molecular interactions across all three axes of limb development. Old models have evolved with acquisition of molecular knowledge, and in more recent times mathematical modeling approaches have been invoked to explain the precise spatio-temporal regulation of gene networks that coordinate limb patterning and outgrowth. This review focuses on recent advances in our understanding of vertebrate limb development, highlighting the signaling interactions required to lay down the pattern on which the processes of differentiation will act to ultimately produce the final limb.

  14. Ultrasound imaging in lower limb prosthetics.

    PubMed

    Douglas, Tania; Solomonidis, Stephan; Sandham, William; Spence, William

    2002-03-01

    The biomechanical interaction between the residual limb and the prosthetic socket determines the quality of fit of the socket in lower limb prosthetics. An understanding of this interaction and the development of quantitative measures to predict the quality of fit of the socket are important for optimal socket design. Finite-element modeling is used widely for biomechanical modeling of the limb/socket interaction and requires information on the internal and external geometry of the residual limb. Volumetric imaging methods such as X-ray computed tomography, magnetic resonance imaging, and ultrasound have been used to obtain residual limb shape information. Of these modalities, ultrasound has been introduced most recently and its development for visualization in prosthetics is the least mature. This paper reviews ultrasound image acquisition and processing methods as they have been applied in lower limb prosthetics.

  15. Mangling upper limb injuries in industry.

    PubMed

    Ring, D; Jupiter, J B

    1999-01-01

    The salvage of upper limbs mangled by industrial machinery became possible with the development of predictable techniques of vascular and microvascular anastamosis. Unfortunately, many of these salvaged limbs are associated with fair and poor functional outcomes. The quality of the skeletal fixation can have a substantial effect on the functional outcome and should be a major focus of the limb repair process. Internal plate fixation facilitates wound care and limb mobilization without tethering muscle-tendon units and is safe in the majority of severe upper limb injuries provided that all devitalized tissue is debrided and, if necessary, reconstructed using microvascular tissue transfers. Injury patterns, especially those which involve associated injury of the elbow or forearm ligaments, must be identified and treated appropriately. Internal fixation should restore anatomical alignment and provide sufficient stability to allow immediate active mobilization of the limb without contributing to devascularization of the soft tissues or skeleton.

  16. New concepts in lower limb orthotics.

    PubMed

    Loke, M

    2000-08-01

    Lower limb orthotics is in the process of a default transformation because of its association with lower limb prosthetics, a mechanical discipline that has translated component and material innovations into balance and velocity function gains to achieve a level of ambulation not possible a generation ago. This article discusses the fundamental mechanical similarities and differences of lower limb orthotics to prosthetics and their application to orthoses designed to improve the gait outcome of patients requiring orthotic intervention.

  17. Treatment of acute lower limb ischaemia.

    PubMed

    Lukasiewicz, Aleksander

    2016-01-01

    Acute lower limb ischaemia poses a major threat to limb survival. For many years surgical thromboembolectomy was the mainstay of treatment. Recent years have brought an endovascular revolution in the management of acute lower limb ischaemia. A wide range of endovascular procedures can nowadays be employed, providing results at least as good as the traditional surgical approach. This paper is an overview of currently utilised endovascular options as well as recent modifications of standard surgical techniques.

  18. Gas gangrene in the diabetic foot: lessons learned from a salvaged limb.

    PubMed

    Aerden, D; Lipsky, B A; Denecker, N; Nieboer, K; Keymeulen, B

    2014-01-01

    A 55 year old man was seen in the emergency department with an infected right foot and sepsis. Examination of the right foot revealed subcutaneous crepitus from the metatarsal head up to the tarsus; interstitial and intramedullary gas was confirmed on x-rays and computed tomographic scans. During 44 days of hospitalization, the patient was treated with multiple courses of antibiotic therapy, various wound care modalities (including negative wound pressure therapy) and several surgical interventions (debridements, amputations, revascularizations and reconstructive plastic surgery). Although limb salvage was ultimately accomplished, in retrospect many management decisions were suboptimal. A critical reassessment of our approach to this patient allowed us to identify several areas for improvement and this audit provided us an opportunity to learn from managing this difficult case.

  19. Critical Limb Ischemia: Reporting Outcomes and Quality

    PubMed Central

    2012-01-01

    The impetus to pursue quality in limb salvage is high in the current economic environment. This has been spurred on by the diffusion of multiple technologies, the lack of well-defined cost-effectiveness benchmarks, and the paucity of process and structure benchmarks. Furthermore, no national database exists to capture current activity and trends, and lead structure and process changes that could analyze outcomes and improve standards in peripheral interventions for limb salvage. This manuscript examines the challenges in measuring outcomes and quality in limb salvage and explores the components necessary for ensuring quality in limb salvage interventions. PMID:23342183

  20. Endovascular Techniques in Limb Salvage: Stents

    PubMed Central

    El-Sayed, Hosam F.

    2013-01-01

    In patients with critical limb ischemia, the first-line approach for limb salvage has shifted over the past decade from bypass surgery to endovascular intervention. Stenting for the treatment of lower-extremity arterial occlusive disease is an important tool and continues to evolve, with new stent designs and technologies that have been developed to provide superior patency rates and limb salvage. In this article, we discuss the role of peripheral stenting in the treatment of patients with critical limb ischemia, including a review of the relevant current literature and the future directions of such interventions. PMID:23805339

  1. Heparin Reduced Mortality and Sepsis in Severely Burned Children

    PubMed Central

    Zayas, G.J.; Bonilla, A.M.; Saliba, M.J

    2007-01-01

    Summary Objectives. In El Salvador, before 1999, morbidity and mortality in severely burned children were high. In 1998, all children with burns of 40% or larger size died and sepsis was found. With heparin use in 1999, some similarly burned children survived, and sepsis, pain, procedures, and scars were noted to be less. This retrospective study presents the details. Methods. A study was conducted at the National Children's Hospital in El Salvador of all children with burns over 20% size treated in 1998, when no heparin was used, and in 1999, when heparin was added to burns treatment, using an ethics committee approved protocol in use in twelve other countries. Sodium aqueous heparin solution USP from an intestinal source was infused intravenously and applied topically onto burn surfaces and within blisters for the first 1-3 days post-burn. Then heparin, in diminishing doses, was continued only topically until healing. The treatments in 1998 and 1999 were otherwise the same, except that fewer procedures were needed in 1999. Results. There were no significant differences in gender, age, weight, burn aetiology, or burn size between the burned children in 1998 and those in 1999. Burn pain was relieved and pain medicine was not needed in children treated with heparin in 1999. In 1998, one child survived who had a 35% size burn, and the eight children died who had burns of 40% and over. The survival rate was one out of nine (11%). The average burn size was 51.7%. With heparin use in 1999, six of the ten children survived burns of 50.7% average size. The increase in survival with heparin from 11% to 60% and, therefore, the decrease in mortality from 89% to 40% were significant (p < 0.04). Clinical symptoms and positive blood cultures documented bacterial sepsis in the nine children in 1998. In 1999, the blood cultures for sepsis were positive in the four children who died and negative in the six who survived. The nine versus four differences in the incidence of sepsis

  2. Metabolomics with Nuclear Magnetic Resonance Spectroscopy in a Drosophila melanogaster Model of Surviving Sepsis

    PubMed Central

    Bakalov, Veli; Amathieu, Roland; Triba, Mohamed N.; Clément, Marie-Jeanne; Reyes Uribe, Laura; Le Moyec, Laurence; Kaynar, Ata Murat

    2016-01-01

    Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel Drosophila melanogaster model of surviving sepsis using Nuclear Magnetic Resonance (NMR), to determine metabolite profiles. We used a model of percutaneous infection in Drosophila melanogaster to mimic sepsis. We had three experimental groups: sepsis survivors (infected with Staphylococcus aureus and treated with oral linezolid), sham (pricked with an aseptic needle), and unmanipulated (positive control). We performed metabolic measurements seven days after sepsis. We then implemented metabolites detected in NMR spectra into the MetExplore web server in order to identify the metabolic pathway alterations in sepsis surviving Drosophila. Our NMR metabolomic approach in a Drosophila model of recovery from sepsis clearly distinguished between all three groups and showed two different metabolomic signatures of inflammation. Sham flies had decreased levels of maltose, alanine, and glutamine, while their level of choline was increased. Sepsis survivors had a metabolic signature characterized by decreased glucose, maltose, tyrosine, beta-alanine, acetate, glutamine, and succinate. PMID:28009836

  3. MKK3 regulates mitochondrial biogenesis and mitophagy in sepsis-induced lung injury.

    PubMed

    Mannam, Praveen; Shinn, Amanda S; Srivastava, Anup; Neamu, Radu F; Walker, Wendy E; Bohanon, Michael; Merkel, Jane; Kang, Min-Jong; Dela Cruz, Charles S; Ahasic, Amy M; Pisani, Margaret A; Trentalange, Mark; West, A Phillip; Shadel, Gerald S; Elias, Jack A; Lee, Patty J

    2014-04-01

    Sepsis is a systemic inflammatory response to infection and a major cause of death worldwide. Because specific therapies to treat sepsis are limited, and underlying pathogenesis is unclear, current medical care remains purely supportive. Therefore targeted therapies to treat sepsis need to be developed. Although an important mediator of sepsis is thought to be mitochondrial dysfunction, the underlying molecular mechanism is unclear. Modulation of mitochondrial processes may be an effective therapeutic strategy in sepsis. Here, we investigated the role of the kinase MKK3 in regulation of mitochondrial function in sepsis. Using clinically relevant animal models, we examined mitochondrial function in primary mouse lung endothelial cells exposed to LPS. MKK3 deficiency reduces lethality of sepsis in mice and by lowering levels of lung and mitochondrial injury as well as reactive oxygen species. Furthermore, MKK3 deficiency appeared to simultaneously increase mitochondrial biogenesis and mitophagy through the actions of Sirt1, Pink1, and Parkin. This led to a more robust mitochondrial network, which we propose provides protection against sepsis. We also detected higher MKK3 activation in isolated peripheral blood mononuclear cells from septic patients compared with nonseptic controls. Our findings demonstrate a critical role for mitochondria in the pathogenesis of sepsis that involves a previously unrecognized function of MKK3 in mitochondrial quality control. This mitochondrial pathway may help reveal new diagnostic markers and therapeutic targets against sepsis.

  4. Specific elevation of DcR3 in sera of sepsis patients and its potential role as a clinically important biomarker of sepsis

    PubMed Central

    Kim, Sunghee; Mi, Lijun; Zhang, Lurong

    2012-01-01

    Because of its potentially important role in the pathogenesis of sepsis, the expression of soluble decoy receptor 3 (DcR3) was investigated in sera of sepsis patients. The serum levels of DcR3 and its TNF-like ligand TL1A and homologous decoy receptor OPG were quantified by ELISA. The values of DcR3 to diagnose sepsis were analyzed by receiver-operating characteristic (ROC) curves. The results showed that DcR3 was significantly elevated in sepsis compared to SIRS (systemic inflammatory response syndrome), a condition similar to sepsis but resulting from noninfectious insults. DcR3 showed superior area under the ROC curve (AUC, 0.958) compared to poor AUCs of TL1A and OPG. At a cut-off of 3.24 ng/ml, DcR3 predicted sepsis from SIRS with 96% sensitivity and 82.6% specificity. DcR3 also predicted sepsis from cancer and inflammatory bowel disease with equally excellent values. Therefore, DcR3 serum level has the potential to serve as a reliable biomarker of sepsis. PMID:22647538

  5. Extracellular Control of Limb Regeneration

    NASA Astrophysics Data System (ADS)

    Calve, S.; Simon, H.-G.

    Adult newts possess the ability to completely regenerate organs and appendages. Immediately after limb loss, the extracellular matrix (ECM) undergoes dramatic changes that may provide mechanical and biochemical cues to guide the formation of the blastema, which is comprised of uncommitted stem-like cells that proliferate to replace the lost structure. Skeletal muscle is a known reservoir for blastema cells but the mechanism by which it contributes progenitor cells is still unclear. To create physiologically relevant culture conditions for the testing of primary newt muscle cells in vitro, the spatio-temporal distribution of ECM components and the mechanical properties of newt muscle were analyzed. Tenascin-C and hyaluronic acid (HA) were found to be dramatically upregulated in the amputated limb and were co-expressed around regenerating skeletal muscle. The transverse stiffness of muscle measured in situ was used as a guide to generate silicone-based substrates of physiological stiffness. Culturing newt muscle cells under different conditions revealed that the cells are sensitive to both matrix coating and substrate stiffness: Myoblasts on HA-coated soft substrates display a rounded morphology and become more elongated as the stiffness of the substrate increases. Coating of soft substrates with matrigel or fibronectin enhanced cell spreading and eventual cell fusion.

  6. [Critical limb ischemia--update].

    PubMed

    Melamed, Eitan; Kotyba, Baydousi; Galili, Offer; Karmeli, Ron

    2010-12-01

    Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery occlusive disease. Without timely diagnosis and revascularization, patients with CLI are at risk of devastating complications including loss of limb and life. Therapeutic goals in treating patients with CLI include reducing cardiovascular risk factors, relieving ischemic pain, heating ulcers, preventing major amputation, improving quality of life and increasing survival. These aims may be achieved through medical therapy, revascularization or amputation. The past decade has seen substantial growth in endovascular therapies and options now exist for treating long segment occlusive disease, but surgical bypass may still yield more durable results. Patients who are younger, more active, and at low risk for surgery, may have better outcomes undergoing an operation. This is also indicated for endovascular failures, which may include technical failures or late occlusions after stents or other procedures. In contrast, frail patients with a limited life expectancy may experience better outcomes with endovascular therapy. For patients who are non-ambulatory, demented, or unfit to undergo revascularization, an amputation should be considered.

  7. Sepsis in the Pediatric Cardiac Intensive Care Unit

    PubMed Central

    Wheeler, Derek S.; Jeffries, Howard E.; Zimmerman, Jerry J.; Wong, Hector R.; Carcillo, Joseph A.

    2012-01-01

    The survival rate for children with congenital heart disease (CHD) has increased significantly coincident with improved techniques in cardiothoracic surgery, cardiopulmonary bypass, and myocardial protection, and post-operative care. Cardiopulmonary bypass, likely in combination with ischemia-reperfusion injury, hypothermia, and surgical trauma, elicits a complex, systemic inflammatory response that is characterized by activation of the complement cascade, release of endotoxin, activation of leukocytes and the vascular endothelium, and release of pro-inflammatory cytokines. This complex inflammatory state causes a transient immunosuppressed state, which may increase the risk of hospital-acquired infection in these children. Postoperative sepsis occurs in nearly 3% of children undergoing cardiac surgery and significantly increases length of stay in the pediatric cardiac intensive care unit as well as the risk for mortality. Herein, we review the epidemiology, pathobiology, and management of sepsis in the pediatric cardiac intensive care unit. PMID:22337571

  8. Right Ventricle Failure in Sepsis: A Case Report

    PubMed Central

    Lakshmanadoss, Umashankar; Levitan, Bryana M; Hsi, David H

    2011-01-01

    Sepsis could produce myocardial depression and typically it affects the left ventricle (LV). Sepsis could also affect right ventricle (RV), in addition to the interdependence with LV. RV pressure may be elevated secondary to pulmonary vasoconstriction, leading to RV dysfunction. Unlike LV, RV is poorly prepared to compensate for acute overload. Aggressive volume replacement may be vital to maintain RV function, but excess hydration can cause RV dilation, decreased LV diastolic filling, and reduced cardiac output. In patients having signs of inadequate cardiac output even after initial volume resuscitation, RV function should be assessed with echocardiogram. If RV dysfunction is noted, then fluid therapy should be guided by CVP measurements. If cardiac output increases with increasing CVP, maintaining higher filling pressures on the right side is indicated. On the other hand, increasing CVP with worsening of the cardiac output could worsen the RV dysfunction. In addition to the fluid management, treatment of other reversible causes like acidosis and hypoxia is also a key.

  9. Association between sepsis and Rocky Mountain spotted fever.

    PubMed

    Bacci, Marcelo Rodrigues; Namura, José Jorge

    2012-12-06

    Rocky Mountain spotted fever (RMSF) is a disease caused by the Gram-negative coccobacillus Rickettsia ricketsii which has been on the rise since the last decade in the USA. The symptoms are common to the many viral diseases, and the classic triad of fever, rash and headache is not always present when RMSF is diagnosed. It may progress to severe cases such as renal failure, disseminated intravascular coagulation and septicaemia. This report aims to present a fulminant case of RMSF associated with sepsis. It describes a female patient's case that quickly progressed to sepsis and death. The patient showed non-specific symptoms for 5 days before being admitted to a hospital. The fact that she lived in an area highly infested with Amblyomma aureolatum ticks was unknown to the medical staff until the moment she died.

  10. Host response to Candida albicans bloodstream infection and sepsis

    PubMed Central

    Duggan, Seána; Leonhardt, Ines; Hünniger, Kerstin; Kurzai, Oliver

    2015-01-01

    Candida albicans is a major cause of bloodstream infection which may present as sepsis and septic shock - major causes of morbidity and mortality world-wide. After invasion of the pathogen, innate mechanisms govern the early response. Here, we outline the models used to study these mechanisms and summarize our current understanding of innate immune responses during Candida bloodstream infection. This includes protective immunity as well as harmful responses resulting in Candida induced sepsis. Neutrophilic granulocytes are considered principal effector cells conferring protection and recognize C. albicans mainly via complement receptor 3. They possess a range of effector mechanisms, contributing to elimination of the pathogen. Neutrophil activation is closely linked to complement and modulated by activated mononuclear cells. A thorough understanding of these mechanisms will help in creating an individualized approach to patients suffering from systemic candidiasis and aid in optimizing clinical management. PMID:25785541

  11. Successful treatment of Chromobacterium violaceum sepsis in South Africa.

    PubMed

    Bosch, F J; Badenhorst, L; Le Roux, J A; Louw, V J

    2008-10-01

    Chromobacterium violaceum sepsis is extremely rare and usually fatal. A very few cases of C. violaceum infection have been reported from Africa, but never from South Africa. As far as could be ascertained, this infection has never been reported in a patient with leukaemia. We describe what we believe to be the first such case of C. violaceum sepsis, in a 16-year-old female patient with acute biphenotypic leukaemia, which developed during the neutropenic phase after intensive chemotherapy. The infection was due to a non-pigmented strain of C. violaceum and was associated with a co-infection with Candida parapsilosis; both were successfully treated using broad-spectrum antibiotics, antifungals and removal of a Hickman line.

  12. Disseminated toxoplasmosis presenting as sepsis in two AIDS patients.

    PubMed

    Barbosa, Carlos José Dornas Gonçalves; Molina, Rodrigo Juliano; de Souza, Murilo Barcelos; Silva, Ana Cristina A; Micheletti, Adilha Rua; dos Reis, Marlene Antonia; de Paula Antunes Teixeira, Vicente; Silva-Vergara, Mario León

    2007-01-01

    This report describes two patients who presented acute disseminated and severe toxoplasmosis as the first opportunistic disease related to acquired immunodeficiency syndrome. At admission, clinical and laboratory findings were similar to sepsis or septic shock and a fast evolutive course to death occurred in both cases. At necropsy, an inflammatory reaction and presence of a great number of Toxoplasma gondii cysts and tachyzoites were observed in most organs examined.

  13. Laboratory Diagnosis of Sepsis? No SIRS, Not Just Yet

    PubMed Central

    2015-01-01

    In order to maximize the benefit of prompt antimicrobial therapy and avoid the risk associated with inappropriate use of antimicrobial agents, patients with suspected sepsis must be rapidly differentiated from patients with systemic inflammatory response syndrome (SIRS). In combination with standard microbiological testing, a number of biomarkers have been recently evaluated for this purpose, and the performance characteristics of the most promising of these are reviewed. PMID:25631808

  14. Laboratory Diagnosis of Sepsis? No SIRS, Not Just Yet.

    PubMed

    Dunne, W Michael

    2015-08-01

    In order to maximize the benefit of prompt antimicrobial therapy and avoid the risk associated with inappropriate use of antimicrobial agents, patients with suspected sepsis must be rapidly differentiated from patients with systemic inflammatory response syndrome (SIRS). In combination with standard microbiological testing, a number of biomarkers have been recently evaluated for this purpose, and the performance characteristics of the most promising of these are reviewed.

  15. Early onset neonatal sepsis: diagnostic dilemmas and practical management.

    PubMed

    Bedford Russell, A R; Kumar, R

    2015-07-01

    Early onset neonatal sepsis is persistently associated with poor outcomes, and incites clinical practice based on the fear of missing a treatable infection in a timely fashion. Unnecessary exposure to antibiotics is also hazardous. Diagnostic dilemmas are discussed in this review, and suggestions offered for practical management while awaiting a more rapidly available 'gold standard' test; in an ideal world, this test would be 100% sensitive and 100% specific for the presence of organisms.

  16. Surviving sepsis--a 3D integrative educational simulator.

    PubMed

    Ježek, Filip; Tribula, Martin; Kulhánek, Tomáš; Mateják, Marek; Privitzer, Pavol; Šilar, Jan; Kofránek, Jiří; Lhotská, Lenka

    2015-08-01

    Computer technology offers greater educational possibilities, notably simulation and virtual reality. This paper presents a technology which serves to integrate multiple modalities, namely 3D virtual reality, node-based simulator, Physiomodel explorer and explanatory physiological simulators employing Modelica language and Unity3D platform. This emerging tool chain should allow the authors to concentrate more on educational content instead of application development. The technology is demonstrated through Surviving sepsis educational scenario, targeted on Microsoft Windows Store platform.

  17. Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic?

    PubMed Central

    de Lima, Lúcio Flávio Peixoto

    2016-01-01

    Despite the advances made in monitoring and treatment of sepsis and septic shock, many septic patients ultimately develop multiple organ dysfunction (MODS) and die, suggesting that other players are involved in the pathophysiology of this syndrome. Mitochondrial dysfunction occurs early in sepsis and has a central role in MODS development. MODS severity and recovery of mitochondrial function have been associated with survival. In recent clinical and experimental investigations, mitochondrion-target therapy for sepsis and septic shock has been suggested to reduce MODS severity and mortality. This intervention, which might be named “metabolic resuscitation”, would lead to improved mitochondrial activity afforded by pharmacological and nutritional agents. Of particular interest in this therapeutic strategy is thiamine, a water-soluble vitamin that plays an essential role in cellular energy metabolism. Critical illness associated with hypermetabolic states may predispose susceptible individuals to the development of thiamine deficiency, which is not usually identified by clinicians as a source of lactic acidosis. The protective effects of thiamine on mitochondrial function may justify supplementation in septic patients at risk of deficiency. Perspectives of supplementation with other micronutrients (ascorbic acid, tocopherol, selenium and zinc) and potential metabolic resuscitators [coenzyme Q10 (CoQ10), cytochrome oxidase (CytOx), L-carnitine, melatonin] to target sepsis-induced mitochondrial dysfunction are also emerging. Metabolic resuscitation may probably be a safe and effective strategy in the treatment of septic shock in the future. However, until then, preliminary investigations should be replicated in further researches for confirmation. Better identification of groups of patients presumed to benefit clinically by a certain intervention directed to “mitochondrial resuscitation” are expected to increase driven by genomics and metabolomics. PMID:27501325

  18. Clavanin bacterial sepsis control using a novel methacrylate nanocarrier.

    PubMed

    Saúde, Amanda C M; Ombredane, Alicia S; Silva, Osmar N; Barbosa, João A R G; Moreno, Susana E; Araujo, Ana Claudia Guerra; Falcão, Rosana; Silva, Luciano P; Dias, Simoni C; Franco, Octávio L

    2014-01-01

    Controlling human pathogenic bacteria is a worldwide problem due to increasing bacterial resistance. This has prompted a number of studies investigating peptides isolated from marine animals as a possible alternative for control of human pathogen infections. Clavanins are antimicrobial peptides isolated from the marine tunicate Styela clava, showing 23 amino acid residues in length, cationic properties, and also high bactericidal activity. In spite of clear benefits from the use of peptides, currently 95% of peptide properties have limited pharmaceutical applicability, such as low solubility and short half-life in the circulatory system. Here, nanobiotechnology was used to encapsulate clavanin A in order to develop nanoantibiotics against bacterial sepsis. Clavanin was nanostructured using EUDRAGIT(®) L 100-55 and RS 30 D solution (3:1 w:w). Atomic force, scanning electron microscopy and dynamic light scattering showed nanoparticles ranging from 120 to 372 nm in diameter, with a zeta potential of -7.16 mV and a polydispersity index of 0.123. Encapsulation rate of 98% was assessed by reversed-phase chromatography. In vitro bioassays showed that the nanostructured clavanin was partially able to control development of Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Furthermore, nanostructures did not show hemolytic activity. In vivo sepsis bioassays were performed using C57BL6 mice strain inoculated with a polymicrobial suspension. Assays led to 100% survival rate under sub-lethal sepsis assays and 40% under lethal sepsis assays in the presence of nanoformulated clavanin A until the seventh day of the experiment. Data here reported indicated that nanostructured clavanin A form shows improved antimicrobial activity and has the potential to be used to treat polymicrobial infections.

  19. Clavanin bacterial sepsis control using a novel methacrylate nanocarrier

    PubMed Central

    Saúde, Amanda CM; Ombredane, Alicia S; Silva, Osmar N; Barbosa, João ARG; Moreno, Susana E; Guerra Araujo, Ana Claudia; Falcão, Rosana; Silva, Luciano P; Dias, Simoni C; Franco, Octávio L

    2014-01-01

    Controlling human pathogenic bacteria is a worldwide problem due to increasing bacterial resistance. This has prompted a number of studies investigating peptides isolated from marine animals as a possible alternative for control of human pathogen infections. Clavanins are antimicrobial peptides isolated from the marine tunicate Styela clava, showing 23 amino acid residues in length, cationic properties, and also high bactericidal activity. In spite of clear benefits from the use of peptides, currently 95% of peptide properties have limited pharmaceutical applicability, such as low solubility and short half-life in the circulatory system. Here, nanobiotechnology was used to encapsulate clavanin A in order to develop nanoantibiotics against bacterial sepsis. Clavanin was nanostructured using EUDRAGIT® L 100-55 and RS 30 D solution (3:1 w:w). Atomic force, scanning electron microscopy and dynamic light scattering showed nanoparticles ranging from 120 to 372 nm in diameter, with a zeta potential of -7.16 mV and a polydispersity index of 0.123. Encapsulation rate of 98% was assessed by reversed-phase chromatography. In vitro bioassays showed that the nanostructured clavanin was partially able to control development of Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Furthermore, nanostructures did not show hemolytic activity. In vivo sepsis bioassays were performed using C57BL6 mice strain inoculated with a polymicrobial suspension. Assays led to 100% survival rate under sub-lethal sepsis assays and 40% under lethal sepsis assays in the presence of nanoformulated clavanin A until the seventh day of the experiment. Data here reported indicated that nanostructured clavanin A form shows improved antimicrobial activity and has the potential to be used to treat polymicrobial infections. PMID:25382976

  20. Prevalence and risk factors of sepsis-induced cardiomyopathy

    PubMed Central

    Sato, Ryota; Kuriyama, Akira; Takada, Tadaaki; Nasu, Michitaka; Luthe, Sarah Kyuragi

    2016-01-01

    Abstract The aim of the study is to evaluate the epidemiology and clinical features of sepsis-induced cardiomyopathy (SICM). A retrospective cohort study was conducted. A total of 210 adult patients with sepsis or septic shock admitted to a Japanese tertiary care hospital from January 1, 2013, to December 31, 2015, who underwent transthoracic echocardiography (TTE) on admission. The definition of SICM was ejection fraction (EF) < 50% and a ≥10% decrease compared to the baseline EF which recovered within 2 weeks, in sepsis or septic shock patients. Our primary outcome was the incidence rate of SICM. Our secondary outcomes were the in-hospital mortality rate and length of intensive care unit (ICU) stay according to the presence or absence of SICM. In total, 29 patients (13.8%) were diagnosed with SICM. The prevalence rate of SICM was significantly higher in male than in female (P = 0.02). Multivariate logistic regression analyses revealed that the incidence of SICM was associated with younger age (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95–0.99), higher lactate level on admission (OR, 1.18; 95% CI, 1.05–1.32) and history of heart failure (HF) (OR, 3.77; 95% CI, 1.37–10.40). There were no significant differences in the in-hospital and 30-day mortality between patients with and without SICM (24.1% vs 12.7%, P = 0.15; 20.7% vs 12.1%, P = 0.23). Lengths of hospital and ICU stay were significantly longer in patients with SICM than in those without SICM (median, 43 vs 26 days, P = 0.04; 9 vs 5 days, P < 0.01). SICM developed in 13.8% of patients with sepsis and septic shock. A younger age, higher lactate levels on admission and history of HF were risk factors. PMID:27684877

  1. Extracorporeal therapy in sepsis: are we there yet?

    PubMed

    Shukla, Ashutosh M

    2012-02-01

    The role of extracorporeal therapies (ECTs) in sepsis is unclear and is a strongly debated topic in critical-care medicine. Unfortunately, much of this debate arises because we lack a clear understanding of what defines the stage and severity of the disease, and the pivotal pathophysiological events dictating outcomes. In the absence of this knowledge, ECTs remain among a large group of therapies with high promise but unproven efficacy.

  2. Host response biomarker in sepsis: suPAR detection.

    PubMed

    Giamarellos-Bourboulis, Evangelos J; Georgitsi, Marianna

    2015-01-01

    Recent studies of our group have shown that suPAR may complement APACHE II score for risk assessment in sepsis. suPAR may be measured in serum of patients by an enzyme immunosorbent assay developed by Virogates (suPARnostic™). Production of suPAR from circulating neutrophils and monocytes may be assessed after isolation of neutrophils and monocytes and ex vivo culture. This is followed by measurement of suPAR in culture supernatants.

  3. Fever with multiple organ failure: not always sepsis.

    PubMed

    Davlouros, P A; Velissaris, D; Tsiola, A; Filos, K S; Alexopoulos, D

    2010-11-01

    We present the case of a 52-year-old female admitted with fever and multiple organ failure, initially treated for presumed sepsis. However the combination of multiple organ failure, hyperthermia and vascular instability raised the suspicion of a phaeochromocytoma multisystem crisis. An emergency abdominal ultrasound in the intensive care unit disclosed a large tumour of the right adrenal. Despite specific medical treatment for the presumed adrenal emergency and multiple organ failure, the patient succumbed. Postmortem examination verified the diagnosis of phaeochromocytoma.

  4. Inter-electrode tissue resistance is not affected by tissue oedema when electrically stimulating the lower limb of sepsis patients.

    PubMed

    Durfee, William K; Young, Joseph R; Ginz, Hans F

    2014-05-01

    ICU patients typically are given large amounts of fluid and often develop oedema. The purpose of this study was to evaluate whether the oedema would change inter-electrode resistance and, thus, require a different approach to using non-invasive electrical stimulation of nerves to assess muscle force. Inter-electrode tissue resistance in the lower leg was measured by applying a 300 µs constant current pulse and measuring the current through and voltage across the stimulating electrodes. The protocol was administered to nine ICU patients with oedema, eight surgical patients without oedema and eight healthy controls. No significant difference in inter-electrode resistance was found between the three groups. For all groups, resistance decreased as stimulation current increased. In conclusion, inter-electrode resistance in ICU patients with severe oedema is the same as the resistance in regular surgical patients and healthy controls. This means that non-invasive nerve stimulation devices do not need to be designed to accommodate different resistances when used with oedema patients; however, surface stimulation does require higher current levels with oedema patients because of the increased distance between the skin surface and the targeted nerve or muscle.

  5. Sepsis: Something Old, Something New, and a Systems View

    PubMed Central

    Namas, Rami; Zamora, Ruben; Namas, Rajaie; An, Gary; Doyle, John; Dick, Thomas E.; Jacono, Frank J.; Androulakis, Ioannis P.; Nieman, Gary F.; Chang, Steve; Billiar, Timothy R.; Kellum, John A.; Angus, Derek C.; Vodovotz, Yoram

    2011-01-01

    Sepsisis a clinical syndrome characterized by a multi-system response to a microbial pathogenic insult consisting of a mosaic of interconnected biochemical, cellular, and organ-organ interaction networks. A central thread that connects these responses is inflammation, which, while attempting to defend the body and prevent further harm, causes further damage through the feed-forward, pro-inflammatory effects of damage-associated molecular pattern molecules. In this review, we address the epidemiology and current definitions of sepsis, and focus specifically on the biological cascades that comprise the inflammatory response to sepsis. We suggest that attempts to improve clinical outcomes by targeting specific components of this network have been unsuccessful due to the lack of an integrative, predictive, and individualized systems-based approach to define the time-varying, multi-dimensional state of the patient. We highlight the translational impact of computational modeling and other complex systems approaches as applied to sepsis, including in silico clinical trials, patient-specific models, and complexity-based assessments of physiology. PMID:21798705

  6. Imaging in sepsis-associated encephalopathy--insights and opportunities.

    PubMed

    Stubbs, Daniel J; Yamamoto, Adam K; Menon, David K

    2013-10-01

    Sepsis-associated encephalopathy (SAE) refers to a clinical spectrum of acute neurological dysfunction that arises in the context of sepsis. Although the pathophysiology of SAE is incompletely understood, it is thought to involve endothelial activation, blood-brain barrier leakage, inflammatory cell migration, and neuronal loss with neurotransmitter imbalance. SAE is associated with a high risk of mortality. Imaging studies using MRI and CT have demonstrated changes in the brains of patients with SAE that are also seen in disorders such as stroke. Next-generation imaging techniques such as magnetic resonance spectroscopy, diffusion tensor imaging and PET, as well as experimental imaging modalities, provide options for early identification of patients with SAE, and could aid in identification of pathophysiological processes that represent possible therapeutic targets. In this Review, we explore the recent literature on imaging in SAE, relating the findings of these studies to pathological data and experimental studies to obtain insights into the pathophysiology of sepsis-associated neurological dysfunction. Furthermore, we suggest how novel imaging technologies can be used for early-stage proof-of-concept and proof-of-mechanism translational studies, which may help to improve diagnosis in SAE.

  7. Sepsis and Immunosenescence in the Elderly Patient: A Review

    PubMed Central

    Martín, Silvia; Pérez, Alba; Aldecoa, Cesar

    2017-01-01

    Sepsis is a prevalent, serious medical condition with substantial mortality and a significant consumption of health-care resources. Its incidence has increased around 9% annually in general population over the last years and specially in aged patients group. Several risk factors such as comorbidities, preadmission status, malnutrition, frailty, and an impared function in the immune system called immunosenescence are involved in the higher predisposition to sepsis in the elderly patients. Immunosenescence status consists in a functional impairment in both cell-mediated immunity and humoral immune responses and increases not only the risk for develop sepsis but also lead to more severe presentation of infection and may be is also related with a higher mortality. There is a also a concern about to admit patients in the intensive care units taking into account that the outcome of elderly patients is poorer compared to younger people. Nevertheless, the management of septic elderly patients does not differ substantially from younger people. In addition, the quality of life in septic elderly survivors is also lower than in younger people. But age, as alone factor, should not be used to determine treatment options because the poorer outcomes is thought to be due to the increased comorbidities and frailty in this group of patients. PMID:28293557

  8. The role of genetics and antibodies in sepsis

    PubMed Central

    Giamarellos-Bourboulis, Evangelos J.

    2016-01-01

    During the course of sepsis when immunosuppression predominates, the concentrations of circulating immunoglobulins (IGs) are decreased and this is associated with adverse outcomes. The production of IGs as response to invasive bacterial pathogens takes place through a complex pathway starting from the recognition of the antigen (Ag) by innate immune cells that process and present Ags to T cells. The orchestration of T-helper (Th) lymphocyte responses directs specific B cells and ends with the production of IGs by plasma cells. All molecules implicated in this process are encoded by genes bearing single nucleotide polymorphisms (SNPs). Meta-analysis of case-control studies have shown that the carriage of minor frequency SNPs of CD14, TLR2 and TNF is associated with increased sepsis risk. The ambiguity of results of clinical trials studying the clinical efficacy of exogenous IG administration in sepsis suggests that efficacy of treatment should be considered after adjustment for SNPs of all implicated genes in the pathway of IG production. PMID:27713886

  9. Zwitterionic chitosan for the systemic treatment of sepsis

    PubMed Central

    Cho, Eun Jung; Doh, Kyung-Oh; Park, Jinho; Hyun, Hyesun; Wilson, Erin M.; Snyder, Paul W.; Tsifansky, Michael D.; Yeo, Yoon

    2016-01-01

    Severe sepsis and septic shock are life-threatening conditions, with Gram-negative organisms responsible for most sepsis mortality. Systemic administration of compounds that block the action of lipopolysaccharide (LPS), a constituent of the Gram-negative outer cell membrane, is hampered by their hydrophobicity and cationic charge, the very properties responsible for their interactions with LPS. We hypothesize that a chitosan derivative zwitterionic chitosan (ZWC), previously shown to suppress the production of pro-inflammatory cellular mediators in LPS-challenged macrophages, will have protective effects in an animal model of sepsis induced by systemic injection of LPS. In this study, we evaluate whether ZWC attenuates the fatal effect of LPS in C57BL/6 mice and investigate the mechanism by which ZWC counteracts the LPS effect using a PMJ2-PC peritoneal macrophage cell line. Unlike its parent compound with low water solubility, intraperitoneally administered ZWC is readily absorbed with no local residue or adverse tissue reaction at the injection site. Whether administered at or prior to the LPS challenge, ZWC more than doubles the animals’ median survival time. ZWC appears to protect the LPS-challenged organisms by forming a complex with LPS and thus attenuating pro-inflammatory signaling pathways. These findings suggest that ZWC have utility as a systemic anti-LPS agent. PMID:27412050

  10. Pro-Resolving Molecules—New Approaches to Treat Sepsis?

    PubMed Central

    Buechler, Christa; Pohl, Rebekka; Aslanidis, Charalampos

    2017-01-01

    Inflammation is a complex response of the body to exogenous and endogenous insults. Chronic and systemic diseases are attributed to uncontrolled inflammation. Molecules involved in the initiation of inflammation are very well studied while pathways regulating its resolution are insufficiently investigated. Approaches to down-modulate mediators relevant for the onset and duration of inflammation are successful in some chronic diseases, while all of them have failed in sepsis patients. Inflammation and immune suppression characterize sepsis, indicating that anti-inflammatory strategies alone are inappropriate for its therapy. Heme oxygenase 1 is a sensitive marker for oxidative stress and is upregulated in inflammation. Carbon monoxide, which is produced by this enzyme, initiates multiple anti-inflammatory and pro-resolving activities with higher production of omega-3 fatty acid-derived lipid metabolites being one of its protective actions. Pro-resolving lipids named maresins, resolvins and protectins originate from the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid while lipoxins are derived from arachidonic acid. These endogenously produced lipids do not simply limit inflammation but actively contribute to its resolution, and thus provide an opportunity to combat chronic inflammatory diseases and eventually sepsis. PMID:28241480

  11. Forsythoside B protects against experimental sepsis by modulating inflammatory factors.

    PubMed

    Jiang, Wang-Lin; Yong-Xu; Zhang, Shu-Ping; Zhu, Hai-Bo; Jian-Hou

    2012-07-01

    The present study investigated the effects of Forsythoside B on an experimental model of sepsis induced by caecal ligation and puncture (CLP) in rats and elucidated the potential mechanism in cultured RAW 264.7 cells. Results showed that Forsythoside B concentration-dependently down-regulated the levels of TNF-α, IL-6 and high-mobility group-box 1 protein (HMGB1) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, inhibited the IκB kinase (IKK) pathway and modulated nuclear factor (NF)- κB. Intravenous injection (i.v.) of Forsythoside B alone or plus Imipenem reduced serum levels of TNF-α, IL-6, HMGB1, triggering receptor expressed on myeloid cells (TREM-1) and endotoxin, while the serum level of IL-10 was up-regulated and myeloperoxidase (MPO) in lung, liver and small intestine was reduced. Meanwhile, i.v. of Forsythoside B alone or plus Imipenem reduced CLP-induced lethality in rats. These data indicated that the antisepsis effect of Forsythoside B is mediated by decreasing local and systemic levels of a wide spectrum of inflammatory mediators. Its antisepsis mechanism may be that Forsythoside B binds to LPS and reduces the biological activity of serum LPS, and inhibits NF-κB activition. Our studies enhance the case for the use of Forsythoside B in sepsis. Forsythoside B itself has promise as a therapy for the treatment of sepsis in humans.

  12. Evaluating the Near-Term Infant for Early Onset Sepsis

    PubMed Central

    Jordan, Jeanne A.; Durso, Mary Beth; Butchko, Allyson R.; Jones, Judith G.; Brozanski, Beverly S.

    2006-01-01

    Although the rate of early onset sepsis in the near-term neonate is low (one to eight of 1000 cases), the rate of mortality and morbidity is high. As a result, infants receive multiple, broad-spectrum antibiotic therapy, many for up to 7 days despite blood cultures showing no growth. Maternal intrapartum antibiotic prophylaxis and small blood volume collections from infants are cited as reasons for the lack of confidence in negative culture results. Incorporating an additional, more rapid test could facilitate a more timely diagnosis in these infants. To this end, a 16S rDNA polymerase chain reaction (PCR) assay was compared to blood culturing for use as a tool in evaluating early onset sepsis. Of 1751 neonatal intensive care unit admissions that were screened, 1233 near-term infants met inclusion criteria. Compared to culture, PCR demonstrated excellent analytical specificity (1186 of 1216, 97.5%) and negative predictive value (1186 of 1196, 99.2%); however, PCR failed to detect a significant number of culture-proven cases. These findings underscore the cautionary stance that should be taken at this time when considering the use of a molecular amplification test for diagnosing neonatal sepsis. The experience gained from this study illustrates the need for changes in sample collection and preparation techniques so as to improve analytical sensitivity of the assay. PMID:16825509

  13. Unfractionated heparin attenuates intestinal injury in mouse model of sepsis by inhibiting heparanase

    PubMed Central

    Chen, Song; Zhang, Xiaojuan; Sun, Yini; Hu, Ziwei; Lu, Siyu; Ma, Xiaochun

    2015-01-01

    Intestinal injury is a key feature in sepsis. Heparanase, a heparin sulfate-specific glucuronidase, mediates the onset of organ injury during early sepsis. Heparin has the function to attenuate inflammation and injury induced by multiple factors; however, whether unfractionated heparin (UFH) can attenuate the intestinal injury induced by sepsis as well as the underlying mechanism is still unknown. In the present study, the function of UFH in intestinal injury induced by sepsis was explored. Results of our study showed that after CLP operation, the inflammatory response and expression of heparanase were increased and NF-κB and MAPK P38 signaling pathways were activated. However, pretreatment with UFH will inhibit the expression and activation of heparanase, and reverse the activation of NF-κB and MAPK P38 signaling pathways, thus attenuating inflammatory responses induced by sepsis. These results suggest that UFH may be a promising therapeutic drug for intestinal injury caused by sepsis. PMID:26191183

  14. Immunomodulation in sepsis: the role of endotoxin removal by polymyxin B-immobilized cartridge.

    PubMed

    Esteban, Elisabeth; Ferrer, Ricard; Alsina, Laia; Artigas, Antonio

    2013-01-01

    Severe sepsis results in high morbidity and mortality. Immunomodulation strategies could be an adjunctive therapy to treat sepsis. Endotoxin is a component of gram-negative bacteria and plays an important role in the pathogenesis of septic shock when it is recognized by immune cells. Removal of endotoxin could be an effective adjunctive approach to the management of sepsis. Devices to adsorb endotoxin or inflammatory cytokines have been designed as a strategy to treat severe sepsis, especially sepsis caused by gram-negative bacteria. Polymyxin B-immobilized cartridge has been successfully used to treat patients with sepsis of abdominal origin. Although this cartridge was conceived to adsorb endotoxin, several other immunological mechanisms have been elucidated, and this device has also yielded promising results in patients with nonseptic respiratory failure. In this paper, we summarize the immune modulation actions of Polymyxin B-immobilized cartridge to explore its potential usefulness beyond endotoxin elimination.

  15. Postadmission sepsis as a screen for quality problems: a case-control study.

    PubMed

    Hughes, John S; Eisenhandler, Jon; Goldfield, Norbert; Weinberg, Patti G; Averill, Richard

    2014-01-01

    The present on admission (POA) indicator used with diagnosis codes listed in hospital discharge abstracts makes it possible to screen for possible in-hospital complications, which may in turn point to quality of care problems. A case-control study was performed among 382 patients from 30 New York State hospitals to see if lapses in quality were associated with the development of postadmission sepsis. Cases with hospital-acquired sepsis (labeled not POA) were compared with matched controls without sepsis. The authors found that central venous catheters and emergently inserted peripheral intravenous catheters were associated with subsequent development of sepsis. Urethral catheters were associated with sepsis for medical patients but not for surgical patients. Adherence to several process of care guidelines was incomplete but none occurred statistically significantly more frequently among sepsis cases than controls. Using discharge abstract diagnosis codes to determine the presence of postadmission complications shows promise for identifying areas for quality improvement.

  16. The Floating Upper Limb: Multiple Injuries Involving Ipsilateral, Proximal, Humeral, Supracondylar, and Distal Radial Limb.

    PubMed

    Manaan, Qazi; Bashir, Adil; Zahoor, Adnan; Mokhdomi, Taseem A; Danish, Qazi

    2016-09-01

    Floating arm injury represents a common yet complicated injury of the childhood severely associated with limb deformation and even morbidity, if not precisely addressed and credibly operated. Here, we report a rare floating upper limb case of a 9-year-old boy with multiple injuries of ipsilateral proximal humeral, supracondylar and distal radial limb. This is the first report to document such a combined floating elbow and floating arm injury in the same limb. In this report, we discuss the surgical procedures used and recovery of the patient monitored to ascertain the effectiveness of the method in limb reorganisation.

  17. The Floating Upper Limb: Multiple Injuries Involving Ipsilateral, Proximal, Humeral, Supracondylar, and Distal Radial Limb

    PubMed Central

    Manaan, Qazi; Bashir, Adil; Zahoor, Adnan; Mokhdomi, Taseem A.

    2016-01-01

    Floating arm injury represents a common yet complicated injury of the childhood severely associated with limb deformation and even morbidity, if not precisely addressed and credibly operated. Here, we report a rare floating upper limb case of a 9-year-old boy with multiple injuries of ipsilateral proximal humeral, supracondylar and distal radial limb. This is the first report to document such a combined floating elbow and floating arm injury in the same limb. In this report, we discuss the surgical procedures used and recovery of the patient monitored to ascertain the effectiveness of the method in limb reorganisation. PMID:27583121

  18. Recipient twin limb ischemia with postnatal onset.

    PubMed

    Broadbent, Roland Spencer

    2007-02-01

    After the occurrence of 3 local cases of limb ischemia in newborn twins, we reviewed the literature to investigate this combination systematically. This review reveals a distinct condition: postnatal onset limb ischemia affecting recipient twins in twin-twin transfusion syndrome.

  19. 21 CFR 890.3475 - Limb orthosis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Limb orthosis. 890.3475 Section 890.3475 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3475 Limb orthosis. (a)...

  20. 21 CFR 890.3475 - Limb orthosis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Limb orthosis. 890.3475 Section 890.3475 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3475 Limb orthosis. (a)...

  1. 21 CFR 890.3475 - Limb orthosis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Limb orthosis. 890.3475 Section 890.3475 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3475 Limb orthosis. (a)...

  2. 21 CFR 890.3475 - Limb orthosis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Limb orthosis. 890.3475 Section 890.3475 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3475 Limb orthosis. (a)...

  3. 21 CFR 890.3475 - Limb orthosis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Limb orthosis. 890.3475 Section 890.3475 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3475 Limb orthosis. (a)...

  4. Newborn with Gastroschisis associated with Limb Anomalies

    PubMed Central

    Win, Phyu Phyu

    2017-01-01

    Gastroschisis is often found together with other extra intestinal conditions such as limb, spine, cardiac, central nervous system and genitourinary abnormalities. There are reports of its association with young maternal age. The cases presented here highlight the association of gastroschisis with limbs anomalies and young maternal age. PMID:28083494

  5. Effect of D-glucose feeding on mortality induced by sepsis

    PubMed Central

    Kim, Sung-Su; Sim, Yun-Beom; Park, Soo-Hyun; Lee, Jae-Ryeong; Sharma, Naveen

    2016-01-01

    Sepsis is the life-threatening response to infection which can lead to tissue damage, organ failure, and death. In the current study, the effect of orally administered D-glucose on the mortality and the blood glucose level induced by D-Galactosamine (GaLN)/lipopolysaccharide (LPS)-induced sepsis was examined in ICR mice. After various amounts of D-glucose (from 1 to 8 g/kg) were orally fed, sepsis was induced by injecting intraperitoneally (i.p.) the mixture of GaLN /LPS. Oral pre-treatment with D-glucose dose-dependently increased the blood glucose level and caused a reduction of sepsis-induced mortality. The oral post-treatment with D-glucose (8 g/kg) up to 3 h caused an elevation of the blood glucose level and protected the mortality observed in sepsis model. However, D-glucose post-treated at 6, 9, or 12 h after sepsis induction did not affect the mortality and the blood glucose level induced by sepsis. Furthermore, the intrathecal (i.t.) pretreatment once with pertussis toxin (PTX; 0.1 µg/5 ml) for 6 days caused a reduction of D-glucose-induced protection of mortality and hyperglycemia. Furthermore, once the hypoglycemic state is continued up to 6 h after sepsis initiated, sepsis-induced mortality could not be reversed by D-glucose fed orally. Based on these findings, it is assumed that the hypoglycemic duration between 3 and 6 h after the sepsis induction may be a critical time of period for the survival. D-glucose-induced protective effect against sepsis-induced mortality appears to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Finally, the production of hyperglycemic state may be critical for the survival against the sepsis-induced mortality. PMID:26807027

  6. [Clostridial sepsis and gas gangrene of the abdominal wall after cholecystectomy].

    PubMed

    Lochman, P; Kabelác, K; Pospísil, I; Dobes, D; Cáp, R

    2007-01-01

    Clostridial sepsis is a rare complication after intraabdominal operations, mostly fatal. According to our knowledge only two papers describing clostridial sepsis as postoperative complication in 4 patients were published in the Czech literature, only one of them survived. Authors present a case report of patient operated on for cholecystolithiasis and obstructive icterus where within 48 hours after cholecystectomy the clostridial sepsis and gas gangrene of the abdominal wall developed and that were successfuly managed.

  7. An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation

    PubMed Central

    Pena, Olga M.; Hancock, David G.; Lyle, Ngan H.; Linder, Adam; Russell, James A.; Xia, Jianguo; Fjell, Christopher D.; Boyd, John H.; Hancock, Robert E.W.

    2014-01-01

    Background Sepsis involves aberrant immune responses to infection, but the exact nature of this immune dysfunction remains poorly defined. Bacterial endotoxins like lipopolysaccharide (LPS) are potent inducers of inflammation, which has been associated with the pathophysiology of sepsis, but repeated exposure can also induce a suppressive effect known as endotoxin tolerance or cellular reprogramming. It has been proposed that endotoxin tolerance might be associated with the immunosuppressive state that was primarily observed during late-stage sepsis. However, this relationship remains poorly characterised. Here we clarify the underlying mechanisms and timing of immune dysfunction in sepsis. Methods We defined a gene expression signature characteristic of endotoxin tolerance. Gene-set test approaches were used to correlate this signature with early sepsis, both newly and retrospectively analysing microarrays from 593 patients in 11 cohorts. Then we recruited a unique cohort of possible sepsis patients at first clinical presentation in an independent blinded controlled observational study to determine whether this signature was associated with the development of confirmed sepsis and organ dysfunction. Findings All sepsis patients presented an expression profile strongly associated with the endotoxin tolerance signature (p < 0.01; AUC 96.1%). Importantly, this signature further differentiated between suspected sepsis patients who did, or did not, go on to develop confirmed sepsis, and predicted the development of organ dysfunction. Interpretation Our data support an updated model of sepsis pathogenesis in which endotoxin tolerance-mediated immune dysfunction (cellular reprogramming) is present throughout the clinical course of disease and related to disease severity. Thus endotoxin tolerance might offer new insights guiding the development of new therapies and diagnostics for early sepsis. PMID:25685830

  8. Immunoinflammatory Response in Critically Ill Patients: Severe Sepsis and/or Trauma

    PubMed Central

    Popovic, Nada; Djordjevic, Dragan

    2013-01-01

    Immunoinflammatory response in critically ill patients is very complex. This review explores some of the new elements of immunoinflammatory response in severe sepsis, tumor necrosis factor-alpha in severe acute pancreatitis as a clinical example of immune response in sepsis, immune response in severe trauma with or without secondary sepsis, and genetic aspects of host immuno-inflammatory response to various insults in critically ill patients. PMID:24371374

  9. New paradigms in sepsis: from prevention to protection of failing microcirculation.

    PubMed

    Hawiger, J; Veach, R A; Zienkiewicz, J

    2015-10-01

    Sepsis, also known as septicemia, is one of the 10 leading causes of death worldwide. The rising tide of sepsis due to bacterial, fungal and viral infections cannot be stemmed by current antimicrobial therapies and supportive measures. New paradigms for the mechanism and resolution of sepsis and consequences for sepsis survivors are emerging. Consistent with Benjamin Franklin's dictum 'an ounce of prevention is worth a pound of cure', sepsis can be prevented by vaccinations against pneumococci and meningococci. Recently, the NIH NHLBI Panel redefined sepsis as 'severe endothelial dysfunction syndrome in response to intravascular and extravascular infections causing reversible or irreversible injury to the microcirculation responsible for multiple organ failure'. Microvascular endothelial injury underlies sepsis-associated hypotension, edema, disseminated intravascular coagulation, acute respiratory distress syndrome and acute kidney injury. Microbial genome products trigger 'genome wars' in sepsis that reprogram the human genome and culminate in a 'genomic storm' in blood and vascular cells. Sepsis can be averted experimentally by endothelial cytoprotection through targeting nuclear signaling that mediates inflammation and deranged metabolism. Endothelial 'rheostats' (e.g. inhibitors of NF-κB, A20 protein, CRADD/RAIDD protein and microRNAs) regulate endothelial signaling. Physiologic 'extinguishers' (e.g. suppressor of cytokine signaling 3) can be replenished through intracellular protein therapy. Lipid mediators (e.g. resolvin D1) hasten sepsis resolution. As sepsis cases rose from 387 330 in 1996 to 1.1 million in 2011, and are estimated to reach 2 million by 2020 in the US, mortality due to sepsis approaches that of heart attacks and exceeds deaths from stroke. More preventive vaccines and therapeutic measures are urgently needed.

  10. The aneurogenic limb identifies developmental cell interactions underlying vertebrate limb regeneration.

    PubMed

    Kumar, Anoop; Delgado, Jean-Paul; Gates, Phillip B; Neville, Graham; Forge, Andrew; Brockes, Jeremy P

    2011-08-16

    The removal of the neural tube in salamander embryos allows the development of nerve-free aneurogenic limbs. Limb regeneration is normally nerve-dependent, but the aneurogenic limb regenerates without nerves and becomes nerve-dependent after innervation. The molecular basis for these tissue interactions is unclear. Anterior Gradient (AG) protein, previously shown to rescue regeneration of denervated limbs and to act as a growth factor for cultured limb blastemal cells, is expressed throughout the larval limb epidermis and is down-regulated by innervation. In an aneurogenic limb, the level of AG protein remains high in the epidermis throughout development and regeneration, but decreases after innervation following transplantation to a normal host. Aneurogenic epidermis also shows a fivefold difference in secretory gland cells, which express AG protein. The persistently high expression of AG in the epithelial cells of an aneurogenic limb ensures that regeneration is independent of the nerve. These findings provide an explanation for this classical problem, and identify regulation of the epidermal niche by innervation as a distinctive developmental mechanism that initiates the nerve dependence of limb regeneration. The absence of this regulation during anuran limb development might suggest that it evolved in relation to limb regeneration.

  11. Limb pain in migraine and cluster headache.

    PubMed Central

    Guiloff, R J; Fruns, M

    1988-01-01

    Upper limb pain occurred in close temporal association with attacks of migraine, cluster headache and cluster-migraine in 22 cases. Seven had also lower limb pain. Limb pain was usually ipsilateral to the headache but could alternate sides and behaved like other accepted migraine accompaniments. It was always ipsilateral to the associated paraesthesiae/numbness (9 cases) and weakness (6 cases). The distribution and restricted localisations of limb pain were similar to those of the sensory symptoms and could not be accounted for by primary dysfunction of the peripheral or autonomic nervous systems. A central origin for limb pain is postulated. A temporary dysfunction in the somatosensory cortex, and/or its thalamic connections, during migraine or cluster headache attacks, might mediate such pain in a number of patients. PMID:3216204

  12. Slow Movements of Bio-Inspired Limbs

    NASA Astrophysics Data System (ADS)

    Babikian, Sarine; Valero-Cuevas, Francisco J.; Kanso, Eva

    2016-10-01

    Slow and accurate finger and limb movements are essential to daily activities, but the underlying mechanics is relatively unexplored. Here, we develop a mathematical framework to examine slow movements of tendon-driven limbs that are produced by modulating the tendons' stiffness parameters. Slow limb movements are driftless in the sense that movement stops when actuations stop. We demonstrate, in the context of a planar tendon-driven system representing a finger, that the control of stiffness suffices to produce stable and accurate limb postures and quasi-static (slow) transitions among them. We prove, however, that stable postures are achievable only when tendons are pretensioned, i.e., they cannot become slack. Our results further indicate that a non-smoothness in slow movements arises because the precision with which individual stiffnesses need to be altered changes substantially throughout the limb's motion.

  13. Planar cell polarity in vertebrate limb morphogenesis.

    PubMed

    Gao, Bo; Yang, Yingzi

    2013-08-01

    Studies of the vertebrate limb development have contributed significantly to understanding the fundamental mechanisms underlying growth, patterning, and morphogenesis of a complex multicellular organism. In the limb, well-defined signaling centers interact to coordinate limb growth and patterning along the three axes. Recent analyses of live imaging and mathematical modeling have provided evidence that polarized cell behaviors governed by morphogen gradients play an important role in shaping the limb bud. Furthermore, the Wnt/planar cell polarity (PCP) pathway that controls uniformly polarized cell behaviors in a field of cells has emerged to be critical for directional morphogenesis in the developing limb. Directional information coded in the morphogen gradient may be interpreted by responding cells through regulating the activities of PCP components in a Wnt morphogen dose-dependent manner.

  14. On stellar limb darkening and exoplanetary transits

    NASA Astrophysics Data System (ADS)

    Howarth, Ian D.

    2011-12-01

    This paper examines how to compare stellar limb-darkening coefficients evaluated from model atmospheres with those derived from photometry. Different characterizations of a given model atmosphere can give quite different numerical results (even for a given limb-darkening 'law'), while light-curve analyses yield limb-darkening coefficients that are dependent on system geometry, and that are not directly comparable to any model-atmosphere representation. These issues are examined in the context of exoplanetary transits, which offer significant advantages over traditional binary-star eclipsing systems in the study of stellar limb darkening. 'Like for like' comparisons between light-curve analyses and new model-atmosphere results, mediated by synthetic photometry, are conducted for a small sample of stars. Agreement between the resulting synthetic-photometry/atmosphere-model (SPAM) limb-darkening coefficients and empirical values ranges from very good to quite poor, even though the targets investigated show only a small dispersion in fundamental stellar parameters.

  15. [Psychological adjustment following lower limb amputation].

    PubMed

    Panyi, Lilla Krisztina; Lábadi, Beatrix

    2015-09-27

    Rehabilitation of lower limb amputees and the fitting of their prosthesis depend highly on the psychological adjustment process and motivational state of the patient. The loss of a limb is extremely challenging and can cause various physical and psychological problems. Depression, anxiety, decreased well-being and quality of life, body image dissatisfaction and changes in self-concept and identity are frequent after lower limb amputation. In the interest of adjustment patients have to cope with the emerging changes and difficulties in their lifes as well as the problems in psychological functioning. It is important for them to accept the alterations in their body and identity, and integrate them in a new self-concept in which process motivation is a fundamental issue. The aim of this article is to review the literature on psychological consequences of lower limb amputation, and to propose an integrative way of rehabilitation for lower limb amputees.

  16. Planar Cell Polarity in vertebrate limb morphogenesis

    PubMed Central

    Gao, Bo; Yang, Yingzi

    2013-01-01

    Studies of the vertebrate limb development have contributed significantly to understanding the fundamental mechanisms underlying growth, patterning and morphogenesis of a complex multicellular organism. In the limb, well-defined signaling centers interact to coordinate limb growth and patterning along the three axes. Recent analyses of live imaging and mathematical modeling have provided evidence that polarized cell behaviors governed by morphogen gradients play an important role in shaping the limb bud. Furthermore, the Wnt/Planar Cell Polarity (PCP) pathway that controls uniformly polarized cellular behaviors in a field of cells has emerged to be critical for directional morphogenesis in the developing limb. Directional information coded in the morphogen gradient may be interpreted by responding cells through regulating the activities of PCP components in a Wnt morphogen dose-dependent manner. PMID:23747034

  17. Molecular basis of vertebrate limb patterning.

    PubMed

    Tickle, Cheryll

    2002-10-15

    Mechanisms of limb development are common to all higher vertebrates. The current understanding of how vertebrate limbs develop comes mainly from studies on chick embryos, which are classical models for experimental manipulation, and mouse embryos, which can be genetically manipulated. Work on chick and mouse embryos is often complementary and has direct implications for human limb development. Analysis has moved to the molecular level, which allows direct links to genetics. Even though genes involved in limb development have been discovered by basic scientists through different routes to that taken by clinical geneticists, many of the same genes have been identified. Thus, the fields of embryology and clinical medicine increasingly converge. The next challenge will be to go back to animal models to begin to dissect how particular gene mutations lead to specific limb phenotypes.

  18. Saunders's framework for understanding limb development as a platform for investigating limb evolution.

    PubMed

    Young, John J; Tabin, Clifford J

    2016-11-11

    John W. Saunders, Jr. made seminal discoveries unveiling how chick embryos develop their limbs. He discovered the apical ectodermal ridge (AER), the zone of polarizing activity (ZPA), and the domains of interdigital cell death within the developing limb and determined their function through experimental analysis. These discoveries provided the basis for subsequent molecular understanding of how vertebrate limbs are induced, patterned, and differentiated. These mechanisms are strongly conserved among the vast diversity of tetrapod limbs suggesting that relatively minor changes and tweaks to the molecular cascades are responsible for the diversity observed in nature. Analysis of the pathway systems first identified by Saunders in the context of animals displaying limb reduction show how alterations in these pathways have resulted in multiple mechanisms of limb and digit loss. Other classes of modification to these same patterning systems are seen at the root of other, novel limb morphological alterations and elaborations.

  19. Threatened limb from stingray injury.

    PubMed

    Shiraev, Timothy P; Marucci, Damian; McMullin, Gabrielle

    2016-01-01

    We present the case of a 43-year-old female who suffered a stingray injury to her left ankle. The sting caused occlusion of the dorsalis pedis artery, causing dry gangrene of the medial forefoot. A below knee amputation was recommended but she was transferred for a second opinion. A Prostaglandin E1 infusion was commenced, resulting in alleviation of pain and improvement in perfusion. Amputation of great and second toes was performed, with the head of the first metatarsal preserved and covered via a cross-over skin flap raised from the contralateral leg. Achilles tendon lengthening was then performed to return the foot to a functional position. This case serves to highlight the utility of prostaglandin infusion, and the requirement for a multidisciplinary approach to critical limb ischemia in order to avoid major amputation.

  20. Sonic Hedgehog Signaling in Limb Development

    PubMed Central

    Tickle, Cheryll; Towers, Matthew

    2017-01-01

    The gene encoding the secreted protein Sonic hedgehog (Shh) is expressed in the polarizing region (or zone of polarizing activity), a small group of mesenchyme cells at the posterior margin of the vertebrate limb bud. Detailed analyses have revealed that Shh has the properties of the long sought after polarizing region morphogen that specifies positional values across the antero-posterior axis (e.g., thumb to little finger axis) of the limb. Shh has also been shown to control the width of the limb bud by stimulating mesenchyme cell proliferation and by regulating the antero-posterior length of the apical ectodermal ridge, the signaling region required for limb bud outgrowth and the laying down of structures along the proximo-distal axis (e.g., shoulder to digits axis) of the limb. It has been shown that Shh signaling can specify antero-posterior positional values in limb buds in both a concentration- (paracrine) and time-dependent (autocrine) fashion. Currently there are several models for how Shh specifies positional values over time in the limb buds of chick and mouse embryos and how this is integrated with growth. Extensive work has elucidated downstream transcriptional targets of Shh signaling. Nevertheless, it remains unclear how antero-posterior positional values are encoded and then interpreted to give the particular structure appropriate to that position, for example, the type of digit. A distant cis-regulatory enhancer controls limb-bud-specific expression of Shh and the discovery of increasing numbers of interacting transcription factors indicate complex spatiotemporal regulation. Altered Shh signaling is implicated in clinical conditions with congenital limb defects and in the evolution of the morphological diversity of vertebrate limbs. PMID:28293554

  1. Sonic Hedgehog Signaling in Limb Development.

    PubMed

    Tickle, Cheryll; Towers, Matthew

    2017-01-01

    The gene encoding the secreted protein Sonic hedgehog (Shh) is expressed in the polarizing region (or zone of polarizing activity), a small group of mesenchyme cells at the posterior margin of the vertebrate limb bud. Detailed analyses have revealed that Shh has the properties of the long sought after polarizing region morphogen that specifies positional values across the antero-posterior axis (e.g., thumb to little finger axis) of the limb. Shh has also been shown to control the width of the limb bud by stimulating mesenchyme cell proliferation and by regulating the antero-posterior length of the apical ectodermal ridge, the signaling region required for limb bud outgrowth and the laying down of structures along the proximo-distal axis (e.g., shoulder to digits axis) of the limb. It has been shown that Shh signaling can specify antero-posterior positional values in limb buds in both a concentration- (paracrine) and time-dependent (autocrine) fashion. Currently there are several models for how Shh specifies positional values over time in the limb buds of chick and mouse embryos and how this is integrated with growth. Extensive work has elucidated downstream transcriptional targets of Shh signaling. Nevertheless, it remains unclear how antero-posterior positional values are encoded and then interpreted to give the particular structure appropriate to that position, for example, the type of digit. A distant cis-regulatory enhancer controls limb-bud-specific expression of Shh and the discovery of increasing numbers of interacting transcription factors indicate complex spatiotemporal regulation. Altered Shh signaling is implicated in clinical conditions with congenital limb defects and in the evolution of the morphological diversity of vertebrate limbs.

  2. Severe Sepsis and Septic Shock Trials (ProCESS, ARISE, ProMISe): What is Optimal Resuscitation?

    PubMed

    Osborn, Tiffany M

    2017-04-01

    Between 2014 and 2015, 3 independent, multicenter, randomized controlled trials evaluated early goal-directed therapy (EGDT) in severe sepsis and septic shock: Protocolized Care for Early Septic Shock (ProCESS) from the United States; Australasian Resuscitation in Sepsis Evaluation (ARISE), and Protocolised Management in Sepsis (ProMISe) in the United Kingdom. All 3 trials confirmed that there was no survival benefit of EGDT compared to usual resuscitation. How should we define usual care for sepsis given these study findings? Furthermore, the definition of sepsis has now been updated. This article reviews key findings of these 3 trials and discusses these important issues in sepsis management.

  3. Management of Critical Limb Ischemia

    PubMed Central

    Kinlay, Scott

    2016-01-01

    Critical limb ischemia (CLI) is a clinical syndrome of ischemic pain at rest or tissue loss, such as non-healing ulcers or gangrene, related to peripheral artery disease. CLI has a high short-term risk of limb loss and cardiovascular events. Non-invasive or invasive angiography help determine the feasibility and approach to arterial revascularization. An “endovascular-first” approach is often advocated based on a lower procedural risk, however, specific patterns of disease may be best treated by open surgical revascularization. Balloon angioplasty and stenting form the backbone of endovascular techniques, with drug-eluting stents and drug-coated balloons offering low rates of repeat revascularization. Combined antegrade and retrograde approaches can increase success in long total occlusions. Below the knee, angiosome-directed angioplasty may lead to greater wound healing, but failing this, any straight line flow into the foot is pursued. Hybrid surgical techniques such as iliac stenting and common femoral endarterectomy are commonly used to reduce operative risk. Lower extremity bypass grafting is most successful with a good quality, long, single-segment autogenous vein of at least 3.5mm diameter. Minor amputations are often required for tissue loss as part of the treatment strategy. Major amputations (at or above the ankle) limit functional independence and their prevention is a key goal of CLI therapy. Medical therapy after revascularization targets risk factors for atherosclerosis and assesses wound healing and new or recurrent flow limiting disease. The ongoing NIH sponsored BEST-CLI study is a randomized trial of the contemporary endovascular versus open surgical techniques in patients with CLI. PMID:26858079

  4. The diagnosis of sepsis revisited - a challenge for young medical scientists in the 21st century.

    PubMed

    Lynn, Lawrence A

    2014-01-02

    In 1991, a well-meaning consensus group of thought leaders derived a simple definition for sepsis which required the breach of only a few static thresholds. More than 20 years later, this simple definition has calcified to become the gold standard for sepsis protocols and research. Yet sepsis clearly comprises a complex, dynamic, and relational distortion of human life. Given the profound scope of the loss of life worldwide, there is a need to disengage from the simple concepts of the past. There is an acute need to develop 21st century approaches which engage sepsis in its true form, as a complex, dynamic, and relational pattern of death.

  5. Bench-to-bedside review: Neonatal sepsis - redox processes in pathogenesis

    PubMed Central

    2012-01-01

    The present review is aimed at elucidating the neonatal 'sepsis redox cycle' - the cascade of inflammatory and redox events involved in the pathogenesis of sepsis in neonates. While adult and neonatal sepses share some common features, there are some substantial differences: higher mortality rates occur in adult sepsis and worse long-term effects are evident in neonatal sepsis survivors. Such epidemiological data may be explained by the lower ability of IL6 and IL8 to activate NF-κB-regulated transcription in neonatal sepsis in comparison to TNF-α, which is involved in the mechanisms of adult sepsis. The activation of NF-κB in neonatal sepsis is further promoted by hydrogen peroxide and results in mitochondrial dysfunction and energy failure as septic neonates experience decreased O2 consumption as well as lower heat production and body temperature in comparison to healthy peers. In neonates, specific organs that are still under development are vulnerable to sepsis-provoked stress, which may lead to brain, lung, and heart injury, as well as vision and hearing impairments. In the light of the processes integrated here, it is clear that therapeutic approaches should also target specific steps in the neonatal 'sepsis redox cycle' in addition to the current therapeutic approach that is mainly focused on pathogen eradication. PMID:22574892

  6. Risk Factors and Prevention of Late Onset Sepsis in Premature Infants

    PubMed Central

    Downey, L Corbin; Smith, P Brian; Benjamin, Daniel K

    2010-01-01

    Late-onset sepsis in premature infants is a major cause of morbidity, mortality, and increased medical costs. Risk factors include low birth weight, low gestational age, previous antimicrobial exposure, poor hand hygiene, and central venous catheters. Methods studied to prevent late-onset sepsis include early feedings, immune globulin administration, prophylactic antimicrobial administration, and improved hand hygiene. In this review, we will outline the risk factors for development of late-onset sepsis and evidence supporting methods for prevention of late-onset sepsis in premature infants. PMID:20116186

  7. Epstein-Barr virus–associated hemophagocytic syndrome mimicking severe sepsis

    PubMed Central

    Spivack, Talya; Chawla, Rashmi; Marik, Paul E

    2008-01-01

    Severe sepsis is amongst the most common reasons for admission to the intensive care unit (ICU) throughout the world and is a common cause of death. The diagnosis of sepsis is usually straightforward, being based on a constellation of clinical and laboratory features. Noninfectious disorders, including pancreatitis, drug reactions, and autoimmune disorders, may cause a systemic inflammatory response that mimics sepsis. We present the case of a 32-year-old male with Epstein-Barr virus-associated hemophagocytic syndrome who presented to the ICU with features of severe sepsis which progressed to multisystem organ failure and death despite aggressive supportive measures. PMID:19561991

  8. Epstein-Barr virus-associated hemophagocytic syndrome mimicking severe sepsis.

    PubMed

    Spivack, Talya; Chawla, Rashmi; Marik, Paul E

    2008-07-01

    Severe sepsis is amongst the most common reasons for admission to the intensive care unit (ICU) throughout the world and is a common cause of death. The diagnosis of sepsis is usually straightforward, being based on a constellation of clinical and laboratory features. Noninfectious disorders, including pancreatitis, drug reactions, and autoimmune disorders, may cause a systemic inflammatory response that mimics sepsis. We present the case of a 32-year-old male with Epstein-Barr virus-associated hemophagocytic syndrome who presented to the ICU with features of severe sepsis which progressed to multisystem organ failure and death despite aggressive supportive measures.

  9. Epidemiological Study of Sepsis in China: Protocol of a Cross-sectional Survey

    PubMed Central

    Yang, Yi; Xie, Jian-Feng; Yu, Kai-Jiang; Yao, Chen; Li, Jian-Guo; Guan, Xiang-Dong; Yan, Jing; Ma, Xiao-Chun; Kang, Yan; Yang, Cong-Shan; Yao, Xiao-Qing; Shang, Hong-Cai; Qiu, Hai-Bo

    2016-01-01

    Background: Sepsis is the leading cause of death among critically ill patients. Herein, we conducted a national survey to provide data on epidemiology and treatment of sepsis in the clinical practice in China, which has no detailed epidemiological data available on sepsis. Methods: This was a prospective cross-sectional survey from December 1, 2015 to January 31, 2016 in all provinces/municipalities of the mainland of China. The primary outcome of this study was the incidence of sepsis, and the secondary outcome was its etiology in China. Patients with sepsis admitted to the Intensive Care Units were included in this study. The demographic, physiological, bacteriological, and therapeutic data of these patients were recorded. The incidence of sepsis was estimated using the data from the sixth census in China, reported by the Chinese National Health and Family Planning Commission and the National Bureau of Statistics as the standard population. The independent risk factors for increased mortality from sepsis were calculated. Conclusions: This study indicated the incidence and outcome of sepsis in China. It also showed the most common etiology of different sites and types of infection, which could guide empiric antibiotic therapy. Moreover, it provided information on the independent risk factors for increased mortality due to sepsis. The findings provide evidence to guide clinical management and may help improve the outcome in septic patients. Trial Registration: ClinicalTrials.gov, NCT02448472; https://clinicaltrials.gov/show/NCT02448472. PMID:27958229

  10. Immunohistochemical detection of CCR2 and CX3CR1 in sepsis-induced lung injury.

    PubMed

    An, Jun-Ling; Ishida, Yuko; Kimura, Akihiko; Tsokos, Michael; Kondo, Toshikazu

    2009-11-20

    Sepsis is a systemic inflammatory disease with high mortality. In the present study, we immunohistochemically examined CCR2 and CX3CR1 expression in sepsis-induced lung injury, and discussed its availability for the postmortem diagnosis of sepsis. Lung samples were obtained from different lung lobes of nine sepsis and eight control cases with postmortem intervals between 12 and 48h. Immunohistochemically, mononuclear cells recruited into the lungs expressed CCR2 and CX3CR1 in both sepsis and non-septic groups. In double-color immunofluorescence analysis, CCR2- or CX3CR1-positive cells could be identified as CD68-positive macrophages. Moreover, most of CD68-positive macrophages expressed both CCR2 and CX3CR1. Morphometrically, the average of CCR2- and CX3CR1-positive macrophages was significantly increased in sepsis group, compared with control group (sepsis vs. control: 41.6+/-1.3% vs. 8.0+/-0.4% in CCR2; 36.2+/-1.3% vs. 9.2+/-0.4% in CX3CR1). These observations implied that CCR2- or CX3CR1-positive macrophages were recruited into the lungs under several pathological conditions. In particular, their recruitment might be more evident in sepsis. Moreover, from the forensic aspects, immunohistochemical detection of CCR2 and CX3CR1 expression in the lungs can be considered as valuable diagnostic tools for the postmortem diagnosis of sepsis.

  11. The New Sepsis Definitions: Implications for the Basic and Translational Research Communities.

    PubMed

    Coopersmith, Craig M; Deutschman, Clifford S

    2017-03-01

    New definitions of sepsis and septic shock were published in early 2016, updating old definitions that have not been revisited since 2001. These new definitions should profoundly affect sepsis research. In addition, these papers present clinical criteria for identifying infected patients who are highly likely to have or to develop sepsis or septic shock. In contrast to previous approaches, these new clinical criteria are evidence based. In this review, two of the authors of the new definitions detail the content of the papers and explore the implications for shock and sepsis researchers.

  12. The diagnosis of sepsis revisited - a challenge for young medical scientists in the 21st century

    PubMed Central

    2014-01-01

    In 1991, a well-meaning consensus group of thought leaders derived a simple definition for sepsis which required the breach of only a few static thresholds. More than 20 years later, this simple definition has calcified to become the gold standard for sepsis protocols and research. Yet sepsis clearly comprises a complex, dynamic, and relational distortion of human life. Given the profound scope of the loss of life worldwide, there is a need to disengage from the simple concepts of the past. There is an acute need to develop 21st century approaches which engage sepsis in its true form, as a complex, dynamic, and relational pattern of death. PMID:24383420

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

    PubMed

    Delano, Matthew J; Ward, Peter A

    2016-11-01

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

  14. Impact of HIV infection on the haemostatic response during sepsis and malaria.

    PubMed

    Huson, Michaëla A M; Kalkman, Rachel; Hoogendijk, Arie J; Alabi, Abraham S; van 't Veer, Cornelis; Grobusch, Martin P; Meijers, Joost C M; van der Poll, Tom

    2016-06-01

    Patients positive for the human immunodeficiency virus (HIV) are more susceptible to sepsis and malaria, two conditions known to activate the coagulation system. As chronic HIV infection also influences haemostatic mechanisms, we determined the influence of HIV co-infection on coagulation, anticoagulation and the endothelium during sepsis or malaria. We performed a prospective observational study in 325 subjects with or without HIV infection (103 with sepsis, 127 with malaria and 95 asymptomatic controls) in an HIV endemic area in Central Africa. We measured plasma biomarkers indicative of activation of distinct haemostatic mechanisms. Sepsis and malaria had similar effects with elevated markers of coagulation, reduced anticoagulation markers and activation of endothelium. In particular, asymptomatic HIV infection reduced the plasma levels of the anticoagulant co-factor free protein S, and increased activation of the vascular endothelium, which were not normalized by combination antiretroviral therapy. HIV co-infection during sepsis and malaria caused more profound changes in free protein S and von Willebrand factor in sepsis and malaria, and ADAMTS13 in sepsis, while not influencing sepsis- or malaria-induced coagulation activation. These results show for the first time that HIV infection augments selective haemostatic changes during sepsis and malaria, which may contribute to the enhanced morbidity of these conditions in HIV patients.

  15. PPARα augments heart function and cardiac fatty acid oxidation in early experimental polymicrobial sepsis.

    PubMed

    Standage, Stephen W; Bennion, Brock G; Knowles, Taft O; Ledee, Dolena R; Portman, Michael A; McGuire, John K; Liles, W Conrad; Olson, Aaron K

    2017-02-01

    Children with sepsis and multisystem organ failure have downregulated leukocyte gene expression of peroxisome proliferator-activated receptor-α (PPARα), a nuclear hormone receptor transcription factor that regulates inflammation and lipid metabolism. Mouse models of sepsis have likewise demonstrated that the absence of PPARα is associated with decreased survival and organ injury, specifically of the heart. Using a clinically relevant mouse model of early sepsis, we found that heart function increases in wild-type (WT) mice over the first 24 h of sepsis, but that mice lacking PPARα (Ppara(-/-)) cannot sustain the elevated heart function necessary to compensate for sepsis pathophysiology. Left ventricular shortening fraction, measured 24 h after initiation of sepsis by echocardiography, was higher in WT mice than in Ppara(-/-) mice. Ex vivo working heart studies demonstrated greater developed pressure, contractility, and aortic outflow in WT compared with Ppara(-/-) mice. Furthermore, cardiac fatty acid oxidation was increased in WT but not in Ppara(-/-) mice. Regulatory pathways controlling pyruvate incorporation into the citric acid cycle were inhibited by sepsis in both genotypes, but the regulatory state of enzymes controlling fatty acid oxidation appeared to be permissive in WT mice only. Mitochondrial ultrastructure was not altered in either genotype indicating that severe mitochondrial dysfunction is unlikely at this stage of sepsis. These data suggest that PPARα expression supports the hyperdynamic cardiac response early in the course of sepsis and that increased fatty acid oxidation may prevent morbidity and mortality.

  16. Reactive oxygen species–associated molecular signature predicts survival in patients with sepsis

    PubMed Central

    Zhou, Tong; Wang, Ting; Slepian, Marvin J.; Garcia, Joe G. N.; Hecker, Louise

    2016-01-01

    Abstract Sepsis-related multiple organ dysfunction syndrome is a leading cause of death in intensive care units. There is overwhelming evidence that oxidative stress plays a significant role in the pathogenesis of sepsis-associated multiple organ failure; however, reactive oxygen species (ROS)–associated biomarkers and/or diagnostics that define mortality or predict survival in sepsis are lacking. Lung or peripheral blood gene expression analysis has gained increasing recognition as a potential prognostic and/or diagnostic tool. The objective of this study was to identify ROS-associated biomarkers predictive of survival in patients with sepsis. In-silico analyses of expression profiles allowed the identification of a 21-gene ROS-associated molecular signature that predicts survival in sepsis patients. Importantly, this signature performed well in a validation cohort consisting of sepsis patients aggregated from distinct patient populations recruited from different sites. Our signature outperforms randomly generated signatures of the same signature gene size. Our findings further validate the critical role of ROSs in the pathogenesis of sepsis and provide a novel gene signature that predicts survival in sepsis patients. These results also highlight the utility of peripheral blood molecular signatures as biomarkers for predicting mortality risk in patients with sepsis, which could facilitate the development of personalized therapies. PMID:27252846

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

    PubMed Central

    Wang, Yifei; Zhang, Yunhua; Jiang, Ronglin

    2017-01-01

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

  18. Alterations in splenic lymphocyte subpopulations and increased mortality from sepsis following anesthesia in mice.

    PubMed

    Hansbrough, J F; Zapata-Sirvent, R L; Bartle, E J; Anderson, J K; Elliott, L; Mansour, M A; Carter, W H

    1985-09-01

    The authors evaluated the potential of a variety of anesthetics in mice to produce subsequent alterations in host defenses. Specific monoclonal antibodies and immunofluorescent microscopy were used to enumerate splenic helper/inducer: suppressor/cytotoxic lymphocyte ratios (HSR), and resistance to bacterial challenge was evaluated by a cecal ligation and puncture (CLP) model. Two hours of anesthesia with the intravenous agents ketamine and pentobarbital and with the inhalational agents isoflurane, enflurane, halothane, and halothane-nitrous oxide, were utilized. All anesthetics produced marked depression in the HSR, measured 24 h postanesthesia (P less than 0.05); with all agents, helper T-cell populations were decreased and suppressor populations increased. The HSR remained depressed 72 h postanesthetic, following both ketamine and halothane anesthesia (P less than 0.05). A dose-response curve was determined with enflurane; increasing the anesthetic time from 1 to 6 h resulted in progressively greater depression of the HSR 24 h later. Changes in lymphocyte subtypes of similar magnitude were found in mice after burn injury or hind limb crush injury and amputation, whereas simple laparotomy did not produce such changes. Serum corticosterone levels were not elevated 24 h post-anesthetic with enflurane, suggesting that the alterations were not nonspecific stress reactions. Resistance to sepsis was determined by measuring survival for 96 h after CLP. With CLP performed 24 h following 2 h anesthesia, mortality was increased from normal: control mortality 36.3%; ketamine 65.0% (P less than 0.023); isoflurane 69.5% (P less than 0.006); enflurane 84.2% (P less than 0.0002).(ABSTRACT TRUNCATED AT 250 WORDS)

  19. The functional anatomy of suggested limb paralysis.

    PubMed

    Deeley, Quinton; Oakley, David A; Toone, Brian; Bell, Vaughan; Walsh, Eamonn; Marquand, Andre F; Giampietro, Vincent; Brammer, Michael J; Williams, Steven C R; Mehta, Mitul A; Halligan, Peter W

    2013-02-01

    Suggestions of limb paralysis in highly hypnotically suggestible subjects have been employed to successfully model conversion disorders, revealing similar patterns of brain activation associated with attempted movement of the affected limb. However, previous studies differ with regard to the executive regions involved during involuntary inhibition of the affected limb. This difference may have arisen as previous studies did not control for differences in hypnosis depth between conditions and/or include subjective measures to explore the experience of suggested paralysis. In the current study we employed functional magnetic resonance imaging (fMRI) to examine the functional anatomy of left and right upper limb movements in eight healthy subjects selected for high hypnotic suggestibility during (i) hypnosis (NORMAL) and (ii) attempted movement following additional left upper limb paralysis suggestions (PARALYSIS). Contrast of left upper limb motor function during NORMAL relative to PARALYSIS conditions revealed greater activation of contralateral M1/S1 and ipsilateral cerebellum, consistent with the engagement of these regions in the completion of movements. By contrast, two significant observations were noted in PARALYSIS relative to NORMAL conditions. In conjunction with reports of attempts to move the paralysed limb, greater supplementary motor area (SMA) activation was observed, a finding consistent with the role of SMA in motor intention and planning. The anterior cingulate cortex (ACC, BA 24) was also significantly more active in PARALYSIS relative to NORMAL conditions - suggesting that ACC (BA 24) may be implicated in involuntary, as well as voluntary inhibition of prepotent motor responses.

  20. TES Limb-Geometry Observations of Aerosols

    NASA Technical Reports Server (NTRS)

    Smith, Michael D.

    2003-01-01

    The Thermal Emission Spectrometer (TES) on-board Mars Global Surveyor (MGS) has a pointing mirror that allows observations in the plane of the orbit anywhere from directly nadir to far above either the forward or aft limbs for details about the TES instrument). Nadir-geometry observations are defined as those where the field-of-view contains the surface of Mars (even if the actual observation is at a high emission angle far from true nadir). Limb-geometry observations are defined as those where the line-of-sight of the observations does not intersect the surface. At a number of points along the MGS orbit (typically every 10 deg. or 20 deg. of latitude) a limb sequence is taken, which includes a stack of overlapping TES spectra from just below the limb to more than 120 km above the limb. A typical limb sequence has approx. 20 individual spectra, and the projected size of a TES pixel at the limb is 13 km.

  1. The mangled limb: salvage versus amputation.

    PubMed

    Wolinsky, Philip R; Webb, Lawrence X; Harvey, Edward J; Tejwani, Nirmal C

    2011-01-01

    A mangled extremity is defined as a limb with injury to three of four systems in the extremity. The decision to salvage or amputate the injured limb has generated much controversy in the literature, with studies to support advantages of each approach. Various scoring systems have proved unreliable in predicting the need for amputation or salvage; however, a recurring theme in the literature is that the key to limb viability seems to be the severity of the soft-tissue injury. Factors such as associated injuries, patient age, and comorbidities (such as diabetes) also should be considered. Attempted limb salvage should be considered only if a patient is hemodynamically stable enough to tolerate the necessary surgical procedures and blood loss associated with limb salvage. For persistently hemodynamically unstable patients and those in extremis, life comes before limb. Recently, the Lower Extremity Assessment Project study attempted to answer the question of whether amputation or limb salvage achieves a better outcome. The study also evaluated other factors, including return-to-work status, impact of the level of and bilaterality of the amputation, and economic cost. There appears to be no significant difference in return to work, functional outcomes, or the cost of treatment (including the prosthesis) between the two groups. A team approach with different specialties, including orthopaedics, plastic surgery, vascular surgery and trauma general surgery, is recommended for treating patients with a mangled extremity.

  2. A rare case of symmetrical four limb gangrene following emergency neurosurgery

    PubMed Central

    Phan, Pho NH; Acharya, Vikas; Parikh, Dhruv; Shad, Amjad

    2015-01-01

    Introduction The authors report a case of symmetrical peripheral gangrene (SPG) following emergency neurosurgery. Presentation of case A 35-year-old female presented to hospital in Thailand with nausea, headache, and subsequent seizures. She was found to have a large intracranial space-occupying lesion with mass effect. Following emergency surgical debulking and decompression, she suffered from severe sepsis with multiple organ failure, treated with high dose intravenous vasopressors and developed secondary gangrene in all four limbs. She was repatriated to the UK with a baseline GCS of 8 and multiple postoperative medical complications. With initial conservative management, the patient made a prolonged but satisfactory progression to recovery prior to semi-elective debridement and selected digit amputation of the gangrene. Discussion This is the first reported case of four limb symmetrical peripheral gangrene following an emergency craniotomy. Conclusion Although rare, SPG is a substantial complication with high mortality and morbidity and therefore should be especially taken into account for emergency intracranial pathologies in neurosurgical patients, particularly if they require emergency surgery. PMID:26406313

  3. Preliminary results of the induced membrane in upper limb. About 6 cases.

    PubMed

    Anoumou, N M; Traoré, M; Kouamé, M; Yepié, A; Varango, G

    2017-02-01

    The aim of this study was to describe the preliminary results after reconstruction of segmental bone defects (SBDs) in the upper limb of six patients. This retrospective study included three men and three women with an average age of 35years (range 18-62years), who had four primary and two secondary SBDs. The average length of the SBD was 4.5 cm (2-10cm). According to the SOFCOT classification, type I (1 case), type II (4 cases) and type III (1 case) defects were identified. The reconstruction involved the humerus in two cases and the forearm bones in four cases. A posterior plaster cast was applied in all patients during the first stage of treatment. Internal fixation was used during the second phrase (five plates, one K-wire). The mean time elapsed between the first and the second stages of treatment was 3 months (2-4 months). At the final follow-up, bone union was obtained in five patients after an average of 4.6 months (4-6 months). The progression was favorable after the first stage of the induced membrane technique. However, two cases of sepsis were observed after the second stage of treatment, one evolving to osteitis that caused graft resorption. The induced membrane technique is a sequential technique used for treating SBDs. It is an alternative method of bone reconstruction in the upper limb.

  4. The Impact of HIV Co-Infection on the Genomic Response to Sepsis

    PubMed Central

    Huson, Michaëla A. M.; Scicluna, Brendon P.; van Vught, Lonneke A.; Wiewel, Maryse A.; Hoogendijk, Arie J.; Cremer, Olaf L.; Bonten, Marc J. M.; Schultz, Marcus J.; Franitza, Marek; Toliat, Mohammad R.; Nürnberg, Peter; Grobusch, Martin P.; van der Poll, Tom

    2016-01-01

    HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis. PMID:26871709

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

    PubMed Central

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

    2016-01-01

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

  6. Utility of C-reactive protein and hematological parameters in the detection of neonatal sepsis.

    PubMed

    Mannan, M A; Shahidullah, M; Noor, M K; Islam, F; Alo, D; Begum, N A

    2010-04-01

    The present study was undertaken to find out and compare the usefulness of C-reactive protein (CRP) and hematological value with the blood culture in the diagnosis of neonatal sepsis. This prospective and cross sectional study was carried out in the Department of Neonatology, Bangabandhu Sheikh Mujib Medical University (BSMMU) during the period of July 2003 to January 2005. One hundred cases of suspected septicemia and fifty of controls were enrolled in this study. Blood was collected for the estimation of CRP, hematological parameters (total leukocyte count, differential count, platelet count) and blood culture from the newborns having suspected sepsis and CRP and hematological parameters from the control. CRP was raised in 72% of cases and 4% of control. Total leukocyte count (TLC) was elevated in a total of 10% cases and only in 4% controls. Leucopenia occurred in 6% cases. In 50% cases of culture proven sepsis there was thrombocytopenia. Sensitivity and specificity of CRP were 78.6%and 62.5% respectively in suspected neonatal sepsis & 92.86% and 36.11% respectively in culture proven sepsis. This study concluded that CRP is most sensitive method (93%) in culture proven sepsis and (79%) in suspected sepsis and its positive predictive value in suspected sepsis amounts to 88%. In this study among the suspected sepsis TLC and its differential count didn't show any positive results significantly but thrombocytopenia was present in 50% cases of culture positive sepsis. Therefore, CRP can be taken as alternate method for the diagnosis of neonatal sepsis specially in developing countries like Bangladesh.

  7. The Impact of HIV Co-Infection on the Genomic Response to Sepsis.

    PubMed

    Huson, Michaëla A M; Scicluna, Brendon P; van Vught, Lonneke A; Wiewel, Maryse A; Hoogendijk, Arie J; Cremer, Olaf L; Bonten, Marc J M; Schultz, Marcus J; Franitza, Marek; Toliat, Mohammad R; Nürnberg, Peter; Grobusch, Martin P; van der Poll, Tom

    2016-01-01

    HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis.

  8. The Mars Express limbs observations database

    NASA Astrophysics Data System (ADS)

    Gondet, Brigitte; Bibring, Jean-Pierre; Montmessin, Franck; Giuranna, Marco; Hoffmann, Harald; Cardesin, Alejandro

    2015-04-01

    The capability to orient Mars Express allows a great diversity of observations modes, in particular nadir and limb. During day and night limb's observations, 4 out of 7 MEX instruments (the spectrometers: SPICAM, OMEGA, PFS and the high-resolution camera HRSC) work together to provide spectra (.12 µm to 45 µm) of the Martian atmosphere, at each altitude step, with the associated image. We will present the limbs database of more than 10 years in orbit with striking results (dust and clouds detached layers, day and night emissions). The database is now accessible to the scientific community via the ESA/PSA website (www.rssd.esa.int/PSA).

  9. A newborn with unilateral limb enlargement.

    PubMed

    Sharma, Shanel; Maino, Anna P F; Husain, Shad M; Adams, Gill G W

    2012-03-01

    On routine neonatal examination, a newborn term male was noted to have unilateral enlargement of the right lower limb, loose thickened red skin over the palm and widening of all the fingers on the right hand. His body was pinker and warmer on the right side compared with the left and he had a right undescended testicle and hypoplastic scrotum. Radiological examination of the lower limbs demonstrated the enlargement of the soft tissue of the right lower limb compared to the left (Fig. 1). Therefore, the diagnosis was unclear from this constellation of findings and an ophthalmic assessment was requested.

  10. Growing models of vertebrate limb development.

    PubMed

    Towers, Matthew; Tickle, Cheryll

    2009-01-01

    The developing limb has been a very influential system for studying pattern formation in vertebrates. In the past, classical embryological models have explained how patterned structures are generated along the two principal axes of the limb: the proximodistal (shoulder to finger) and anteroposterior (thumb to little finger) axes. Over time, the genetic and molecular attributes of these patterning models have been discovered, while the role of growth in the patterning process has been only recently highlighted. In this review, we discuss these recent findings and propose how the various models of limb patterning can be reconciled.

  11. [Effects of phentolamine on haemodynamics of patients with severe sepsis].

    PubMed

    Yang, W; Li, X B; Zhou, Y; Mo, X M

    2017-02-07

    Objective: To explore the effects of phentolamine on hemodynamic of patients with severe sepsis . Methods: From January 2015 to August 2016, using random number table, 59 patients with severe sepsis were divided into research group and the control group by conventional treatment in Department of Emergency, the Second People's Hospital of Nanning City. The patients of the research group were given phentolamine injection. The CI, ITBVI, EVLWI, SVRI of the patients were monitored by PICCO on 6, 12, 24, 48, 72 h before and after treatment. Measuring clearance of blood lactic acid, lactic acid, comparing two groups of blood lactic acid, lactic acid clearance change tendency, 28 d survival rate and time of the two groups in the ICU of patients was observed. Results: CI, SVRI, ITBVI of the research group was increased obviously, and EVLWI decreased obviously(P<0.05 or P<0.01)12, 24, 48, 72 h after treatment. The levels of blood lactic acid, lactic acid clearancef the research group improved better than that of the control group(P<0.05 or P<0.01) after treatment of 12, 24, 48, 72 h time points, especially lactate clearance increased significantly than the control group[(27.2±2.2) mmol/L vs(13.9±3.0) mmol/L, t=8.322, P=0.034]on 6 h. Time in ICU and 28 days rate of the research group was less than the control group[(9.8±3.6)d vs(13.0±4.1)d, P=0.004 ; (22.6% vs 35.7%, P=0.021)]. Conclusion: Phentolamine can significantly improve the early condition of hemodynamic and the survival rates of patients with severe sepsis.

  12. Liver metabolism and glucogenesis in trauma and sepsis.

    PubMed

    Imamura, M; Clowes, G H; Blackburn, G L; O'Donnell, T F; Trerice, M; Bhimjee, Y; Ryan, N T

    1975-06-01

    The relationship of glucogenesis and other energy-requiring functions of the liver to the proteolysis which is characteristic of trauma and sepsis was studied in conscious pigs following laporotomy and after the induction of intraperitoneal sepsis. By means of appropriately placed thermal dilution catheters, portal and hepatic arterial blood flows, hepatic oxygen consumption, glucogenesis, and uptake of the fuel, substrates were measured. No animal was in shock. Despite significant increases of lactate and aminoacids delivered to the liver, the blood concentrations were maintained in the normal range. The rate of glucogenesis was proportional (r equals 0.71) to the sum of the glucogenic precursors (lactate, pyruvate, glycerol, and alanine) taken up by the liver. Higher rates of glucose production were accompanied by elevated blood insulin values. Hepatic oxygen consumption and the uptake of free fatty acids also were related directly to the glucogenic rate, the correlation coefficients being 0.69 and 0.74, respectively. In the absence of shock, the liver function and hepatic energy production remained normal in post-traumatic and septic states. Under the conditions insulin-resistant muscle in the presence of reduced free fatty acid availability mobilize protein to satisfy local energy requirements. Skeletal muscle can oxidize only branch chain aminoacids; other aminoacids, including alanine, are transported to the liver for glucogenesis or other purposed. This concept accounted for failure of glucose infusion to eliminate post-traumatic and septic proteolysis, since alanine is cleared only from blood by conversion in the liver to glucose. Thus it is concluded that in sepsis the release of glucogenic substrates because of altered metabolism in peripheral tissues determines the rate of hepatic glucogenesis. This relationship constitutes an important metabolic homeostatic mechanism.

  13. Cholecystokinin protects rats against sepsis induced by Staphylococcus aureus.

    PubMed

    Zuelli, Fabiana Maria das Graças Corsi; Cárnio, Evelin Capellari; Saia, Rafael Simone

    2014-06-01

    Staphylococcus aureus is a Gram-positive bacteria described as an important causative agent of sepsis. The contact between host leukocytes and bacteria activates the innate immune response. Nitric oxide, tumor necrosis factor (TNF)-α and interleukin (IL)-1β play a key role in increasing microbicidal activity and controlling cell influx into infectious focus. Contrarily, IL-10 acts as an anti-inflammatory cytokine and bacterial killing suppressor. Immunoregulatory properties have also been attributed to hormones, including cholecystokinin (CCK). CCK protects cardiovascular function and inhibits the inflammatory response induced by lipopolysaccharide, product derived from Gram-negative bacteria. Nevertheless, the role of CCK during Gram-positive infection remains a literature gap. Our aims were to investigate whether CCK protects rats against bacterial dissemination during sepsis induced by S. aureus. We determined whether CCK modulates local and systemic inflammatory response, as well as the cell migration into the infectious focus and the bactericidal capacity of leukocytes. Our results revealed that proglumide (nonselective CCK receptor antagonist) pretreated rats showed higher bacterial counts in blood and peritoneal lavage fluid (PLF) and reduced TNF-α and IL-10 levels in PLF. Moreover, the dissemination of S. aureus may be related to the failure of neutrophil and macrophage migration into the peritoneal cavity. Also, CCK improved the phagocytic and bactericidal ability of these inflammatory cells. Noteworthy is that the adoptive transfer of CCK-treated neutrophils and macrophages in septic rats improved immune defense, reducing bacterial number in blood and PLF. All together, our study clearly demonstrates an important protective role of CCK against sepsis induced by S. aureus.

  14. Transducers for ultrasonic limb plethysmography

    NASA Technical Reports Server (NTRS)

    Nickell, W. T.; Wu, V. C.; Bhagat, P. K.

    1983-01-01

    The design, construction, and performance characteristics of ultasonic transducers suitable for limb plethysmography are presented. Both 3-mm-diameter flat-plate and 12-mm-diameter hemispheric ceramic transducers operating at 2 MHz were fitted in 1-mm thick epoxy-resin lens/acoustic-coupling structures and mounted in exercie-EKG electrode housings for placement on the calf using adhesive collars. The effects of transducer directional characteristics on performance under off-axis rotation and the electrical impedances of the transducers were measured: The flat transducer was found to be sensitive to rotation and have an impedance of 800 ohms; the hemispheric transducer, to be unaffected by rotation and have an impedance of 80 ohms. The use of hemispheric transducers as both transmitter and receiver, or of a flat transducer as transmitter and a hemispheric transducer as receiver, was found to produce adequate dimensional measurements, with minimum care in transducer placement, in short-term physiological experiments and long-term (up to 7-day) attachment tests.

  15. Limb lengthening in Turner syndrome.

    PubMed

    Noonan, K J; Leyes, M; Forriol, F

    1997-01-01

    We report the results and complications of eight consecutive patients who underwent bilateral tibial lengthenings for dwarfism associated with Turner syndrome. Lengthening was performed via distraction osteogenesis with monolateral external fixation. Tibias were lengthened an average distance of 9.2 centimeters or 33 percent of the original tibial length. The average total treatment time was 268 days. The overall complication rate was 169 percent for each tibia lengthened and each segment required an average of 1.7 additional procedures. Seven cases (44 percent) required Achilles tendon lengthening and nine cases (56 percent) developed angulation before or after fixator removal; six of these segments required corrective osteotomy for axial malalignment. Two cases (12.5 percent) developed distraction site nonunion and required plating and bone grafting. From this series we conclude that tibial lengthening via distraction osteogenesis can be used to treat disproportionate short stature in patients with Turner syndrome. However, the benefit of a cosmetic increase in height may not compensate for the high complication rate. Efforts to determine the psychosocial and functional benefits of limb lengthening in patients with short stature is necessary to determine the true cost-benefit ratio of this procedure.

  16. Limb lengthening in Turner syndrome.

    PubMed Central

    Noonan, K. J.; Leyes, M.; Forriol, F.

    1997-01-01

    We report the results and complications of eight consecutive patients who underwent bilateral tibial lengthenings for dwarfism associated with Turner syndrome. Lengthening was performed via distraction osteogenesis with monolateral external fixation. Tibias were lengthened an average distance of 9.2 centimeters or 33 percent of the original tibial length. The average total treatment time was 268 days. The overall complication rate was 169 percent for each tibia lengthened and each segment required an average of 1.7 additional procedures. Seven cases (44 percent) required Achilles tendon lengthening and nine cases (56 percent) developed angulation before or after fixator removal; six of these segments required corrective osteotomy for axial malalignment. Two cases (12.5 percent) developed distraction site nonunion and required plating and bone grafting. From this series we conclude that tibial lengthening via distraction osteogenesis can be used to treat disproportionate short stature in patients with Turner syndrome. However, the benefit of a cosmetic increase in height may not compensate for the high complication rate. Efforts to determine the psychosocial and functional benefits of limb lengthening in patients with short stature is necessary to determine the true cost-benefit ratio of this procedure. Images Figure 1a Figure 1b Figure 1c PMID:9234980

  17. Laser Science and Limb Salvage.

    PubMed

    Friedman, Steven G

    2011-12-01

    Harnessing light energy in the form of lasers became possible after the discovery of electricity. Scientists found various uses for lasers beginning in the 1960s. Creating large amounts of pulsed UV light with any device, including a laser, remained difficult until excimer lasers were invented in the following decade. The invention of excimer lasers coincided with the advent of balloon angioplasty, leading physicians to speculate about using laser energy to obliterate obstructing arterial lesions. The first report of laser energy to vaporize an atherosclerotic plaque appeared in 1980. The ensuing decades witnessed dramatic refinements of laser fibers, laser energy sources, and catheter delivery systems. The favorable results achieved with excimer laser angioplasty in the early 2000s led to a renewed interest in this technology and to the current widespread use of these devices to treat peripheral as well as coronary artery disease. This paper provides a review of laser energy principles, traces the history of the use of lasers to treat vascular disease, and reviews the current literature pertaining to laser angioplasty and limb salvage.

  18. Hyperferritinemic Sepsis: An Opportunity for Earlier Diagnosis and Intervention?

    PubMed Central

    Halstead, E. Scott; Rajasekaran, Surender; Fitzgerald, Julie C.; Weiss, Scott L.

    2016-01-01

    We describe a case of an infant with HSV meningitis and septic shock who demonstrated a remarkably high serum ferritin level. Aggressive pediatric intensive care and the administration of high-dose glucocorticoids were not able to reverse the multiple organ dysfunctions. Subsequent autopsy identified the presence of hemophagocytosis, thus the patient fulfilled hemophagocytic lymphohistiocytosis (HLH) criteria post-mortem. This case highlights that serum ferritin may be an important early indicator of mortality in sepsis due to a cytokine storm similar to macrophage activation syndrome and HLH. PMID:27532033

  19. Management of severe sepsis: advances, challenges, and current status.

    PubMed

    Martin-Loeches, Ignacio; Levy, Mitchell M; Artigas, Antonio

    2015-01-01

    The complexity of treating severe sepsis and septic shock has been elucidated in myriad studies, particularly in the past 10 years. The development of clinical guidelines, insight into the effect of bundle elements, and results of clinical trials have brought to light further opportunities and questions in the approach to pharmaceutical interventions for the global challenge to save lives and reduce healthcare costs. Therapeutic interventions including fluid resuscitation, hemodynamic monitoring, glycemic control, corticosteroids, and antimicrobial therapy and stewardship inform outcomes. Research on biomarkers, use of mesenchymal stem cells, blood purification, immunoglobulins, and antioxidative treatments apropos the immune response may soon yield viable therapies.

  20. Neonatal Conjunctivitis Leading to Neonatal Sepsis--A Case Report.

    PubMed

    Dey, A C; Hossain, M I; Dey, S K; Mannan, M A; Shahidullah, M

    2016-01-01

    Neonatal conjunctivitis is the most common occular disease in neonates. Most infections are acquired during vaginal delivery. In spite most of these cases are benign; some of them may progress to systemic complications like loss of vision if left untreated. The authors present a case of a newborn who developed late onset neonatal sepsis from E. coli positive conjunctivitis. The baby was treated with Injection Meropenem and Injection Amikacin for 10 days. The course was uneventful, after that baby responded well and discharged home on 24th day.

  1. Skew flap for staged below-knee amputation in sepsis.

    PubMed

    Matthews, Christopher O; Williams, Ian M; Lewis, Peter; McLain, A David; Twine, Christopher P

    2016-04-01

    Skew flap amputation was first described in the 1980s but was never as popular as the long posterior flap amputation. This report describes a staged below-knee amputation in sepsis, with pus throughout the leg and a lack of skin coverage. One benefit of skew flaps never previously published is the fact that the suture line is not directly over the tibia. Therefore, an open wound or incomplete skin coverage is not as important as in long posterior flaps where it often leads to bone exposure and revision amputation. These benefits were utilized in this case leading to stump healing.

  2. Mechanical ventilation alone, and in the presence sepsis, induces peripheral skeletal muscle catabolism in neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reduced rates of skeletal muscle accretion are a prominent feature of the metabolic response to sepsis in infants and children. Septic neonates often require medical support with mechanical ventilation (MV). The combined effects of MV and sepsis in muscle have not been examined in neonates, in whom ...

  3. Mechanical ventilation and sepsis induce skeletal muscle catabolism in neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reduced rates of skeletal muscle accretion are a prominent feature of the metabolic response to sepsis in infants and children. Septic neonates often require medical support with mechanical ventilation (MV). The combined effects of MV and sepsis in muscle have not been examined in neonates, in whom ...

  4. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolotis in preterm infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lactoferrin, a normal component of human colostrum, milk, tears and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NEC...

  5. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lactoferrin, a normal component of human colostrum, milk, tears, and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NE...

  6. Sepsis and development impede muscle protein synthesis in neonatal pigs by different ribosomal mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In muscle, sepsis reduces protein synthesis (MPS) by restraining translation in neonates and adults. Even though protein accretion decreases with development as neonatal MPS rapidly declines by maturation, the changes imposed by development on the sepsis-associated decrease in MPS have not been desc...

  7. Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis

    PubMed Central

    Margoles, Lindsay M.; Mittal, Rohit; Klingensmith, Nathan J.; Lyons, John D.; Liang, Zhe; Serbanescu, Mara A.; Wagener, Maylene E.

    2016-01-01

    Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-γ, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion. PMID:27861506

  8. Biomarkers of Delirium in a Low-Risk Community-Acquired Pneumonia-Induced Sepsis.

    PubMed

    Tomasi, Cristiane Damiani; Vuolo, Francieli; Generoso, Jaqueline; Soares, Márcio; Barichello, Tatiana; Quevedo, João; Ritter, Cristiane; Dal-Pizzol, Felipe

    2017-01-01

    There are different theories about the pathophysiology of sepsis-associated encephalopathy (SAE), and the majority of our knowledge was derived from critically ill patients. 7In less severe sepsis, it is probable that neuroinflammation can be a major aspect of SAE development. We hypothesized that in non-severe septic patients, blood biomarkers of inflammation, endothelial activation, coagulation, and brain function would be different when compared to patients with and without brain dysfunction. A total of 30 patients presenting with community-acquired pneumonia (CAP)-induced sepsis were included of which 10 (33 %) developed SAE. Eight medical patients admitted to the general ward, except due to sepsis or infection, which developed delirium were included as delirium, non-sepsis group. From all measured biomarkers, only brain-derived neurotrophic factor (BDNF), regulated upon activation normal T cell expressed, and presumably secreted (RANTES), and interleukin (IL)-10 where significantly different when compared to SAE and sepsis groups. In addition, SAE patients presented higher levels of BDNF, vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), platelet-derived growth factor (PDGF)-AB/BB and RANTES when compared to delirium patients. In conclusion, the profile of biomarkers differs between SAE, sepsis, and delirium patients, suggesting that pathways related to SAE are different from delirium and from sepsis itself.

  9. Don't Go Chasing Waterfalls: Excessive Fluid Resuscitation in Severe Sepsis and Septic Shock.

    PubMed

    Chen, Leon

    2016-01-01

    Aggressive fluid resuscitation is the mainstay therapy in modern sepsis management. Its efficacy was demonstrated in the landmark study by Emmanuel Rivers in 2001. However, more recent evidence largely shows that a positive fluid balance increases mortality in critically ill patients with sepsis. This article examines the theoretical benefits of fluid resuscitation and physiological responses to it that may negatively affect patients' outcome.

  10. Increased FGF21 plasma levels in humans with sepsis and SIRS.

    PubMed

    Gariani, Karim; Drifte, Geneviève; Dunn-Siegrist, Irène; Pugin, Jérôme; Jornayvaz, François R

    2013-01-01

    Fibroblast growth factor 21 (FGF21) is a key regulator in glucose and lipid metabolism and its plasma levels have been shown to be increased not only in humans in different situations such as type 2 diabetes, obesity, and nonalcoholic fatty liver disease but also in animal models of sepsis and pancreatitis. FGF21 is considered as a pharmacological candidate in conditions associated with insulin resistance. The aim of this study was to compare FGF21 plasma levels in patients with sepsis, in patients with systemic inflammatory response syndrome (SIRS), and in healthy controls. We measured FGF21 plasma concentrations in 22 patients with established sepsis, in 11 with SIRS, and in 12 healthy volunteers. Here, we show that FGF21 levels were significantly higher in plasma obtained from patients with sepsis and SIRS in comparison with healthy controls. Also, FGF21 levels were significantly higher in patients with sepsis than in those with noninfectious SIRS. FGF21 plasma levels measured at study entry correlated positively with the APACHE II score, but not with procalcitonin levels, nor with C-reactive protein, classical markers of sepsis. Plasma concentrations of FGF21 peaked near the onset of shock and rapidly decreased with clinical improvement. Taken together, these results indicate that circulating levels of FGF21 are increased in patients presenting with sepsis and SIRS, and suggest a role for FGF21 in inflammation. Further studies are needed to explore the potential role of FGF21 in sepsis as a potential therapeutic target.

  11. Early identification and management of patients with severe sepsis and septic shock in the emergency department.

    PubMed

    Keegan, Joshua; Wira, Charles R

    2014-11-01

    Severe sepsis and septic shock have great relevance to Emergency Medicine physicians because of their high prevalence, morbidity, and mortality. Treatment is time-sensitive, depends on early identification risk stratification, and has the potential to significantly improve patient outcomes. In this article, we review the pathophysiology of, and evidence basis for, the emergency department management of severe sepsis and septic shock.

  12. Severe Sepsis and Septic Shock Associated with Chikungunya Virus Infection, Guadeloupe, 2014.

    PubMed

    Rollé, Amélie; Schepers, Kinda; Cassadou, Sylvie; Curlier, Elodie; Madeux, Benjamin; Hermann-Storck, Cécile; Fabre, Isabelle; Lamaury, Isabelle; Tressières, Benoit; Thiery, Guillaume; Hoen, Bruno

    2016-05-01

    During a 2014 outbreak, 450 patients with confirmed chikungunya virus infection were admitted to the University Hospital of Pointe-à-Pitre, Guadeloupe. Of these, 110 were nonpregnant adults; 42 had severe disease, and of those, 25 had severe sepsis or septic shock and 12 died. Severe sepsis may be a rare complication of chikungunya virus infection.

  13. Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neonatal sepsis and necrotizing enterocolitis (NEC) cause significant neonatal mortality and morbidity in spite of appropriate antibiotic therapy. Enhancing host defence and modulating inflammation by using lactoferrin as an adjunct to antibiotics in the treatment of sepsis and/or NEC may improve cl...

  14. [Lactobacillus Rhamnosus sepsis in a preterm infant associated with probiotic integrator use: a case report.

    PubMed

    Molinaro, Manuela; Aiazzi, Massimo; La Torre, Antonio; Cini, Elisabetta; Banfi, Roberto

    2016-09-01

    Preterm infants are at high risk of neonatal sepsis. We report a case of a preterm infant under prophylaxis with Lactobacillus Rhamnosus for necrotizing enterocolitis; the child develops neonatal sepsis by Lactobacillus Rhamnosus. The infection is improved after probiotic withdrawal and had complete remission after 20 days of specific antibiotic therapy.

  15. Sepsis-Related Mortality of Very Low Birth Weight Brazilian Infants: The Role of Pseudomonas aeruginosa

    PubMed Central

    Pereira, Sylvia Maria Porto; de Almeida Cardoso, Maria Helena Cabral; Figuexeds, Ana Lucia; Mattos, Haroldo; Rozembaum, Ronaldo; Ferreira, Vanessa Isidoro; Portinho, Maria Antonieta; Gonçalves, Ana Cristina; da Costa, Elaine Sobral

    2009-01-01

    The aim of this study is to identify risk factors for sepsis-related mortality in low birth weight (<1500 g) infants. We performed retrospective cohort study to investigate risk factors for sepsis-related mortality in all neonates birth weight <1500 g admitted to Level III neonatal intensive care unit, Brazil, April 2001/September 2004. Of the 203 cases, 71 (35%) had sepsis. Of those, gram-positive was identified in 52/87 blood cultures (59.8%), the most common Coagulase-negative Staphylococcus (31/87; 35.5%). Gram-negative was present in 29 of the 87 positive blood cultures (33.3%), with Pseudomonas aeruginosa (8/87; 9.1%), the most frequent agent. Overall 21 of 71 infants with sepsis (29.6%) died. Risk factors for sepsis-related mortality were gestational age ≤28 weeks, birth weight ≤1000 g (9.6 times more often than birth weight >1000 g), five-minute Apgar ≤7, gram-negative sepsis, mechanical ventilation (6.7 times higher than no use), and intravascular catheter. Sepsis-related mortality was due, mainly, to Pseudomonas aeruginosa; birth weight ≤1000 g and mechanical ventilation were strong sepsis-related mortality predictors. PMID:20182631

  16. Are there standardized cutoff values for neutrophil-lymphocyte ratios in bacteremia or sepsis?

    PubMed

    Gürol, Gölnül; Çiftci, İhsan Hakki; Terizi, Huseyin Agah; Atasoy, Ali Rıza; Ozbek, Ahmet; Köroğlu, Mehmet

    2015-04-01

    Bacteremia and sepsis are common causes of morbidity and mortality worldwide, with incorrect or delayed diagnoses being associated with increased mortality. New tests or markers that allow a more rapid and less costly detection of bacteremia and sepsis have been investigated. The aim of this study was to clarify the cutoff value of the neutrophillymphocyte ratio (NLR) according to procalcitonin (PCT) level in the decision-making processes for bacteremia and sepsis. In addition, other white blood cell subgroup parameters, which are assessed in all hospitals, for bacteremia and sepsis were explored. This retrospective study included 1,468 patients with suspected bacteremia and sepsis. Patients were grouped according to the following PCT criteria: levels <0.05 ng/ml (healthy group), 0.05-0.5 ng/ml (local infection group), 0.5-2 ng/ml (systemic infection group), 2-10 ng/ml (sepsis group), and >10 ng/ml (sepsis shock group). One important finding of this study, which will serve as a baseline to measure future progress, is the presence of many gaps in the information on pathogens that constitute a major health risk. In addition, clinical decisions are generally not coordinated, compromising the ability to assess and monitor a situation. This report represents the first study to determine the limits of the use of NLR in the diagnosis of infection or sepsis using a cutoff value of <5 when sufficient exclusion criteria are used.

  17. Computing network-based features from physiological time series: application to sepsis detection.

    PubMed

    Santaniello, Sabato; Granite, Stephen J; Sarma, Sridevi V; Winslow, Raimond L

    2014-01-01

    Sepsis is a systemic deleterious host response to infection. It is a major healthcare problem that affects millions of patients every year in the intensive care units (ICUs) worldwide. Despite the fact that ICU patients are heavily instrumented with physiological sensors, early sepsis detection remains challenging, perhaps because clinicians identify sepsis by using static scores derived from bed-side measurements individually, i.e., without systematically accounting for potential interactions between these signals and their dynamics. In this study, we apply network-based data analysis to take into account interactions between bed-side physiological time series (PTS) data collected in ICU patients, and we investigate features to distinguish between sepsis and non-sepsis conditions. We treated each PTS source as a node on a graph and we retrieved the graph connectivity matrix over time by tracking the correlation between each pair of sources' signals over consecutive time windows. Then, for each connectivity matrix, we computed the eigenvalue decomposition. We found that, even though raw PTS measurements may have indistinguishable distributions in non-sepsis and early sepsis states, the median /I of the eigenvalues computed from the same data is statistically different (p <; 0.001) in the two states and the evolution of /I may reflect the disease progression. Although preliminary, these findings suggest that network-based features computed from continuous PTS data may be useful for early sepsis detection.

  18. Early management of sepsis with emphasis on early goal directed therapy: AME evidence series 002

    PubMed Central

    Hong, Yucai; Smischney, Nathan J.; Kuo, Han-Pin; Tsirigotis, Panagiotis; Rello, Jordi; Kuan, Win Sen; Jung, Christian; Robba, Chiara; Taccone, Fabio Silvio; Leone, Marc; Spapen, Herbert; Grimaldi, David; Van Poucke, Sven; Simpson, Steven Q.; Honore, Patrick M.; Hofer, Stefan; Caironi, Pietro

    2017-01-01

    Severe sepsis and septic shock are major causes of morbidity and mortality in patients entering the emergency department (ED) or intensive care unit (ICU). Despite substantial efforts to improve patient outcome, treatment of sepsis remains challenging to clinicians. In this context, early goal directed therapy (EGDT) represents an important concept emphasizing both early recognition of sepsis and prompt initiation of a structured treatment algorithm. As part of the AME evidence series on sepsis, we conducted a systematic review of all randomized controlled EGDT trials. Focus was laid on the setting (emergency department versus ICU) where EGDT was carried out. Early recognition of sepsis, through clinical or automated systems for early alert, together with well-timed initiation of the recommended therapy bundles may improve patients’ outcome. However, the original “EGDT” protocol by Rivers and coworkers has been largely modified in subsequent trials. Currently, many investigators opt for an “expanded” EGDT (as suggested by the Surviving Sepsis Campaign). Evidence is also presented on the effectiveness of automated systems for early sepsis alert. Early recognition of sepsis and well-timed initiation of the SSC bundle may improve patient outcome. PMID:28275488

  19. Early management of sepsis with emphasis on early goal directed therapy: AME evidence series 002.

    PubMed

    Zhang, Zhongheng; Hong, Yucai; Smischney, Nathan J; Kuo, Han-Pin; Tsirigotis, Panagiotis; Rello, Jordi; Kuan, Win Sen; Jung, Christian; Robba, Chiara; Taccone, Fabio Silvio; Leone, Marc; Spapen, Herbert; Grimaldi, David; Van Poucke, Sven; Simpson, Steven Q; Honore, Patrick M; Hofer, Stefan; Caironi, Pietro

    2017-02-01

    Severe sepsis and septic shock are major causes of morbidity and mortality in patients entering the emergency department (ED) or intensive care unit (ICU). Despite substantial efforts to improve patient outcome, treatment of sepsis remains challenging to clinicians. In this context, early goal directed therapy (EGDT) represents an important concept emphasizing both early recognition of sepsis and prompt initiation of a structured treatment algorithm. As part of the AME evidence series on sepsis, we conducted a systematic review of all randomized controlled EGDT trials. Focus was laid on the setting (emergency department versus ICU) where EGDT was carried out. Early recognition of sepsis, through clinical or automated systems for early alert, together with well-timed initiation of the recommended therapy bundles may improve patients' outcome. However, the original "EGDT" protocol by Rivers and coworkers has been largely modified in subsequent trials. Currently, many investigators opt for an "expanded" EGDT (as suggested by the Surviving Sepsis Campaign). Evidence is also presented on the effectiveness of automated systems for early sepsis alert. Early recognition of sepsis and well-timed initiation of the SSC bundle may improve patient outcome.

  20. Development of limb volume measuring system

    NASA Technical Reports Server (NTRS)

    Bhagat, P. K.; Kadaba, P. K.

    1983-01-01

    The mechanisms underlying the reductions in orthostatic tolerance associated with weightlessness are not well established. Contradictory results from measurements of leg volume changes suggest that altered venomotor tone and reduced blood flow may not be the only contributors to orthostatic intolerance. It is felt that a more accurate limb volume system which is insensitive to environmental factors will aid in better quantification of the hemodynamics of the leg. Of the varous limb volume techniques presently available, the ultrasonic limb volume system has proven to be the best choice. The system as described herein is free from environmental effects, safe, simple to operate and causes negligible radio frequency interference problems. The segmental ultrasonic ultrasonic plethysmograph is expected to provide a better measurement of limb volume change since it is based on cross-sectional area measurements.

  1. Ways Children Adjust to Limb Loss

    MedlinePlus

    ... March/April 2006 Original article by Douglas G. Smith, MD Translated into plain language by Helen Osborne ... Limb Deficiencies: Issues and Expectations,” by Douglas G. Smith, MD and Kellye Campbell, RN, ARNP published in ...

  2. CONGENITAL DEFORMITIES OF THE UPPER LIMBS.

    PubMed Central

    Bisneto, Edgard Novaes França

    2015-01-01

    This article, divided into three parts, had the aims of reviewing the most common upper-limb malformations and describing their treatments. In this first part, failure of formation is discussed. The bibliography follows after the first part. PMID:27047864

  3. Limb Loss in Children: Prosthetic Issues

    MedlinePlus

    ... adults with limb loss. Meeting a world-class swimmer, for instance, shows children that they can do ... they won’t ever be the world’s fastest swimmers, children can learn that there is greatness inside ...

  4. Skeletal muscle dedifferentiation during salamander limb regeneration.

    PubMed

    Wang, Heng; Simon, András

    2016-10-01

    Salamanders can regenerate entire limbs throughout their life. A critical step during limb regeneration is formation of a blastema, which gives rise to the new extremity. Salamander limb regeneration has historically been tightly linked to the term dedifferentiation, however, with refined research tools it is important to revisit the definition of dedifferentiation in the context. To what extent do differentiated cells revert their differentiated phenotypes? To what extent do progeny from differentiated cells cross lineage boundaries during regeneration? How do cell cycle plasticity and lineage plasticity relate to each other? What is the relationship between dedifferentiation of specialized cells and activation of tissue resident stem cells in terms of their contribution to the new limb? Here we highlight these problems through the case of skeletal muscle.

  5. Spatial Coupling Affects Both Homologous and Non-Homologous Limbs

    ERIC Educational Resources Information Center

    Huh, Carey Y.

    2004-01-01

    The present study examined the interaction between limb movements in space. The amount of interaction was measured by how much moving one limb affected the movement of another limb. Participants were 24 right-handed university students (19 female, mean AGE=19 years). The task was to draw lines with the right hand while moving another limb in lines…

  6. Isolated primary lymphedema tarda of the upper limb.

    PubMed

    Shariati, Farzaneh; Ravari, Hasan; Kazemzadeh, Gholamhossein; Sadeghi, Ramin

    2013-03-01

    Primary lymphedema tarda is considered as a congenital disease with late presentation. Primary lymphedema tarda usually affects lower limbs, and primary lymphedema tarda of the upper limbs usually accompanies lower limb lymphedema. In the current case report, we present an 80-year-old male patient with isolated left upper limb swelling that lymphoscintigraphy imaging proved to be lymphedema.

  7. PTSD in Limb Trauma and Recovery

    DTIC Science & Technology

    2008-10-16

    self-report and performance-based measures; 2) To test a new scoring system for the Prosthetic Evaluation Questionnaire (PEQ); 3) To determine if...13 “ANALYSIS OF GAIT MECHANICS OF AMPUTEES USING A NEW LOWER LIMB PROSTHESIS ” CONCLUSION...of the first lower limb prosthesis with a powered, biomimetic ankle. ANNUAL REPORT 9/17/2008 VIRTUAL REALITY AND MOTION ANALYSIS TO

  8. Procession to Pediatric Bacteremia and Sepsis: A Series of Covert Operations and Failures in Diplomacy

    PubMed Central

    Bateman, Stacey L.; Seed, Patrick C.

    2011-01-01

    Despite advances in diagnosis and treatment, bacterial sepsis remains a major cause of pediatric morbidity and mortality, particularly among neonates, the critically ill, and the growing immunocompromised patient population. Sepsis is the endpoint of a complex and dynamic series of events in which both host and microbial factors drive the high morbidity and potentially lethal physiological alterations. This article provides a succinct overview of the events that lead to pediatric bloodstream infections (BSI) and sepsis, with a focus on the molecular mechanisms employed by bacteria to subvert host barriers and local immunity to gain access to and persist within the systemic circulation. In the events preceding and during BSI and sepsis, gram-positive and gram-negative pathogens employ a battery of factors for translocation, inhibition of immunity, molecular mimicry, intracellular survival, and nutrient scavenging. Gaps in understanding the molecular pathogenesis of bacterial BSI and sepsis are highlighted as opportunities to identify and develop new therapeutics. PMID:20566606

  9. Predicting treatment failure in severe sepsis and septic shock: looking for the Holy Grail

    PubMed Central

    2013-01-01

    Procalcitonin has been proposed as a specific biomarker of bacterial infections and has been related to the severity of sepsis. The prognostic ability of the initial concentrations of procalcitonin in sepsis is controversial. Some studies find higher initial concentrations in non-survivors but others find no differences. Prognostic assessment based on follow-up of procalcitonin levels may be better than evaluation of the initial levels of procalcitonin. The persistence of elevated procalcitonin levels is indicative of poor prognosis and is associated with mortality. Procalcitonin kinetics could be a tool for assessing the evolution of severe sepsis and sepsis shock. Procalcitonin should find its place as a biomarker for predicting treatment failure of severe sepsis and septic shock. PMID:24004571

  10. Genomics and pharmacogenomics of sepsis: so close and yet so far.

    PubMed

    Russell, James A

    2016-07-07

    Sapru et al. show in this issue of Critical Care that variants of thrombomodulin and the endothelial protein C receptor, but not protein C, are associated with mortality and organ dysfunction (ventilation-free and organ failure-free days) in ARDS. Hundreds of gene variants have been found prognostic in sepsis. However, none of these prognostic genomic biomarkers are used clinically. Predictive biomarker discovery (pharmacogenomics) usually follows a candidate gene approach, utilizing knowledge of drug pathways. Pharmacogenomics could be applied to enhance efficacy and safety of drugs used for treatment of sepsis (e.g., norepinephrine, epinephrine, vasopressin, and corticosteroids). Pharmacogenomics can enhance drug development in sepsis, which is very important because there is no approved drug for sepsis. Pharmacogenomics biomarkers must pass three milestones: scientific, regulatory, and commercial. Huge challenges remain but great opportunities for pharmacogenomics of sepsis are on the horizon.

  11. [Serum lactate as a biomarker of severe sepsis in children with cancer, neutropenia and fever].

    PubMed

    Pacheco-Rosas, Daniel Octavio; Huelgas-Plaza, Ana Celia; Miranda-Novales, María Guadalupe

    2014-01-01

    INTRODUCCIÓN: la neutropenia es una complicación frecuente secundaria a la quimioterapia en los pacientes con cáncer, en quienes la prevalencia de sepsis es de 12.9 a 17.4 % y la letalidad es de 16 %. El objetivo de este estudio fue determinar la utilidad del lactato como biomarcador de sepsis grave en niños con cáncer, fiebre y neutropenia. MÉTODOS: se realizó un estudio de prueba diagnóstica fase II. Se midieron los niveles del lactato al ingreso. Los episodios de neutropenia se clasificaron en tres grupos: I, con sepsis II, sin sepsis; III, pacientes neutropénicos sin fiebre (controles). Se calculó sensibilidad, especificidad, valores predictivos positivo y negativo e índices de verosimilitud. El estándar de oro fue el diagnóstico clínico de sepsis grave.

  12. Evaluation of musculoskeletal sepsis with indium-111 white blood cell imaging

    SciTech Connect

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

    1987-08-01

    The detection of musculoskeletal sepsis, especially following joint replacement, continues to be a challenging problem. Often, even with invasive diagnostic evaluation, the diagnosis of infection remains uncertain. This is a report on the first 55 Indium-111 white blood cell (WBC) images performed in 39 patients for the evaluation of musculoskeletal sepsis. There were 40 negative and 15 positive Indium-111 WBC images. These were correlated with operative culture and tissue pathology, aspiration culture, and clinical findings. Thirty-eight images were performed for the evaluation of possible total joint sepsis (8 positive and 30 negative images); 17 for the evaluation of nonarthroplasty-related musculoskeletal sepsis (7 positive and 10 negative images). Overall, there were 13 true-positive, 39 true-negative, two false-positive, and one false-negative images. Indium-111 WBC imaging is a sensitive and specific means of evaluating musculoskeletal sepsis, especially following total joint replacement.

  13. The effect of HIV infection on the host response to bacterial sepsis.

    PubMed

    Huson, Michaëla A M; Grobusch, Martin P; van der Poll, Tom

    2015-01-01

    Bacterial sepsis is an important cause of morbidity and mortality in patients with HIV. HIV causes increased susceptibility to invasive infections and affects sepsis pathogenesis caused by pre-existing activation and exhaustion of the immune system. We review the effect of HIV on different components of immune responses implicated in bacterial sepsis, and possible mechanisms underlying the increased risk of invasive bacterial infections. We focus on pattern recognition receptors and innate cellular responses, cytokines, lymphocytes, coagulation, and the complement system. A combination of factors causes increased susceptibility to infection and can contribute to a disturbed immune response during a septic event in patients with HIV. HIV-induced perturbations of the immune system depend on stage of infection and are only in part restored by combination antiretroviral therapy. Immunomodulatory treatments currently under development for sepsis might be particularly beneficial to patients with HIV co-infection because many pathogenic mechanisms in HIV and sepsis overlap.

  14. High efficiency binding aptamers for a wide range of sepsis bacterial agents.

    PubMed

    Graziani, Ana Cláudia; Stets, Maria Isabel; Lopes, Ana Luisa Kalb; Schluga, Pedro Henrique Caires; Marton, Soledad; Mendes, Ieda Ferreira; Andrade, Antero Silva Ribeiro de; Krieger, Marco Aurélio; Cardoso, Josiane

    2017-01-24

    Sepsis is a major health problem worldwide, with an extremely high rate of morbidity and mortality, partly due to delayed diagnosis during early disease. Currently, sepsis diagnosis requires bacterial culturing of blood samples over several days, while PCR-based molecular diagnosis methods are faster, but lack sensitivity. The use of biosensors containing nucleic acid aptamers that bind targets with high affinity and specificity could accelerate sepsis diagnosis. Previously, we used Systematic Evolution of Ligands by Exponential Enrichment (SELEX) to develop the aptamers Antibac1 and Antibac2, targeting the ubiquitous bacterial peptidoglycan. Here, we show that these aptamers bind to four Gram-positive and seven Gram-negative bacterial sepsis agents with high binding efficiency. Thus, these aptamers could be used in combination as biological recognition elements in the development of biosensors that are an alternative to rapid bacteria detection, since they could provide culture and amplification-free tests for rapid clinical sepsis diagnosis.

  15. Sepsis Through the Eyes of Proteomics: The Progress in the Last Decade.

    PubMed

    Sharma, Narendra Kumar; Salomao, Reinaldo

    2017-01-01

    Sepsis is a systemic inflammatory response caused by infection whose molecular mechanisms are still not completely understood. The early detection of sepsis remains a great challenge for clinicians because no single biomarker capable of its reliable prediction, hence, delayed diagnosis frequently undermines treatment efforts, thereby contributing to high mortality. There are several experimental approaches used to reveal the molecular mechanism of sepsis progression. Proteomics coupled with mass spectrometry made possible to identify differentially expressed proteins in clinical samples. Recent advancement in liquid chromatography-based separation methods and mass spectrometers resolution and sensitivity with absolute quantitation methods, made possible to use proteomics as a powerful tool for study of clinical samples with higher coverage proteome profiles. In recent years, number of proteomic studies have been done under sepsis and/or in response to endotoxin and showed various signaling pathways, functions, and biomarkers. This review enlightened the proteomic progress in the last decade in sepsis.

  16. Signal transduction induced by activated protein C: no role in protection against sepsis?

    PubMed

    Slofstra, Sjoukje H; ten Cate, Hugo; Spek, C Arnold

    2006-08-01

    The anticoagulant activated protein C (APC) is historically known as a risk factor for venous thrombosis. However, after the positive results of the protein C worldwide evaluation in severe sepsis (PROWESS) trial, which showed that APC was the first drug that considerably reduced sepsis-related mortality, APC is considered a pleiotropic protein with both anticoagulant and anti-inflammatory properties. In addition, in vitro studies have suggested that APC-induced intracellular signal transduction is a potential mechanism by which APC might be protective against sepsis. Recently, however, the efficacy of APC in sepsis has been argued, and also the extent to which the signal transduction capacity of APC contributes to its pro-survival effects is debated. Here, we review the role of APC in the body natural defense against sepsis and discuss the mechanism by which APC might act at a cellular level.

  17. Mathematical modeling of vertebrate limb development.

    PubMed

    Zhang, Yong-Tao; Alber, Mark S; Newman, Stuart A

    2013-05-01

    In this paper, we review the major mathematical and computational models of vertebrate limb development and their roles in accounting for different aspects of this process. The main aspects of limb development that have been modeled include outgrowth and shaping of the limb bud, establishment of molecular gradients within the bud, and formation of the skeleton. These processes occur interdependently during development, although (as described in this review), there are various interpretations of the biological relationships among them. A wide range of mathematical and computational methods have been used to study these processes, including ordinary and partial differential equation systems, cellular automata and discrete, stochastic models, finite difference methods, finite element methods, the immersed boundary method, and various combinations of the above. Multiscale mathematical modeling and associated computational simulation have become integrated into the study of limb morphogenesis and pattern formation to an extent with few parallels in the field of developmental biology. These methods have contributed to the design and analysis of experiments employing microsurgical and genetic manipulations, evaluation of hypotheses for limb bud outgrowth, interpretation of the effects of natural mutations, and the formulation of scenarios for the origination and evolution of the limb skeleton.

  18. An audit of compliance with the sepsis resuscitation care bundle in patients admitted to A&E with severe sepsis or septic shock.

    PubMed

    Baldwin, Lee N; Smith, Sally A; Fender, Veronica; Gisby, Sharon; Fraser, Jayne

    2008-10-01

    Severe sepsis and septic shock are syndromes resulting in a systemic inflammatory response and the dysfunction of one or more organs following infection. The Surviving Sepsis Campaign is an international effort to reduce mortality in severe sepsis and septic shock by 25% by 2009 using a care bundle approach. It comprises evidenced-based interventions to be carried out within 6h of onset of sepsis. We conducted a prospective observational audit of 32 consecutive adult patients with severe sepsis or septic shock admitted via the A&E of a district general hospital. The compliance rate against each element, and overall compliance to the 6-h bundle were obtained. Patients' ages ranged from 55 to 75 years with 53% being male. Overall compliance was 19%. Arterial lactate was undertaken 100% of the time, and only just over half received an appropriate fluid challenge. Administration of an antibiotic was also very slow. Local recommendations include improvements to the track and trigger scoring system in A&E to improve recognition of sick patients, ensuring the doctor responsible for prescribing the antibiotic will administer it, and increasing awareness of the surviving sepsis campaign via education and training of all A&E staff. Given current evidence greater compliance to the care bundle may well improve patient outcomes for this client group.

  19. Clinical course of sepsis, severe sepsis, and septic shock in a cohort of infected patients from ten Colombian hospitals

    PubMed Central

    2013-01-01

    Background Sepsis has several clinical stages, and mortality rates are different for each stage. Our goal was to establish the evolution and the determinants of the progression of clinical stages, from infection to septic shock, over the first week, as well as their relationship to 7-day and 28-day mortality. Methods This is a secondary analysis of a multicenter cohort of inpatients hospitalized in general wards or intensive care units (ICUs). The general estimating equations (GEE) model was used to estimate the risk of progression and the determinants of stages of infection over the first week. Cox regression with time-dependent covariates and fixed covariates was used to determine the factors related with 7-day and 28-day mortality, respectively. Results In 2681 patients we show that progression to severe sepsis and septic shock increases with intraabdominal and respiratory sources of infection [OR = 1,32; 95%IC = 1,20-1,46 and OR = 1.21, 95%CI = 1,11-1,33 respectively], as well as according to Acute Physiology and Chronic Health Evaluation II (APACHE II) [OR = 1,03; 95%CI = 1,02-1,03] and Sequential Organ Failure Assessment (SOFA) [OR = 1,16; 95%CI = 1,14-1,17] scores. The variables related with first-week mortality were progression to severe sepsis [HR = 2,13; 95%CI = 1,13-4,03] and septic shock [HR = 3,00; 95%CI = 1,50-5.98], respiratory source of infection [HR = 1,76; 95%IC = 1,12-2,77], APACHE II [HR = 1,07; 95% CI = 1,04-1,10] and SOFA [HR = 1,09; 95%IC = 1,04-1,15] scores. Conclusions Intraabdominal and respiratory sources of infection, independently of SOFA and APACHE II scores, increase the risk of clinical progression to more severe stages of sepsis; and these factors, together with progression of the infection itself, are the main determinants of 7-day and 28-day mortality. PMID:23883312

  20. Neutrophil Extracellular Traps Induce Organ Damage during Experimental and Clinical Sepsis

    PubMed Central

    Nascimento, Daniele Carvalho; Sônego, Fabiane; Castanheira, Fernanda Vargas e Silva; Melo, Paulo Henrique; Scortegagna, Gabriela Trentin; Silva, Rangel Leal; Barroso-Sousa, Romualdo; Souto, Fabrício Oliveira; Pazin-Filho, Antonio; Figueiredo, Florencio; Alves-Filho, José Carlos; Cunha, Fernando Queiróz

    2016-01-01

    Organ dysfunction is a major concern in sepsis pathophysiology and contributes to its high mortality rate. Neutrophil extracellular traps (NETs) have been implicated in endothelial damage and take part in the pathogenesis of organ dysfunction in several conditions. NETs also have an important role in counteracting invading microorganisms during infection. The aim of this study was to evaluate systemic NETs formation, their participation in host bacterial clearance and their contribution to organ dysfunction in sepsis. C57Bl/6 mice were subjected to endotoxic shock or a polymicrobial sepsis model induced by cecal ligation and puncture (CLP). The involvement of cf-DNA/NETs in the physiopathology of sepsis was evaluated through NETs degradation by rhDNase. This treatment was also associated with a broad-spectrum antibiotic treatment (ertapenem) in mice after CLP. CLP or endotoxin administration induced a significant increase in the serum concentrations of NETs. The increase in CLP-induced NETs was sustained over a period of 3 to 24 h after surgery in mice and was not inhibited by the antibiotic treatment. Systemic rhDNase treatment reduced serum NETs and increased the bacterial load in non-antibiotic-treated septic mice. rhDNase plus antibiotics attenuated sepsis-induced organ damage and improved the survival rate. The correlation between the presence of NETs in peripheral blood and organ dysfunction was evaluated in 31 septic patients. Higher cf-DNA concentrations were detected in septic patients in comparison with healthy controls, and levels were correlated with sepsis severity and organ dysfunction. In conclusion, cf-DNA/NETs are formed during sepsis and are associated with sepsis severity. In the experimental setting, the degradation of NETs by rhDNase attenuates organ damage only when combined with antibiotics, confirming that NETs take part in sepsis pathogenesis. Altogether, our results suggest that NETs are important for host bacterial control and are

  1. Midkine, a multifunctional cytokine, in patients with severe sepsis and septic shock: a pilot study.

    PubMed

    Krzystek-Korpacka, Malgorzata; Mierzchala, Magdalena; Neubauer, Katarzyna; Durek, Grazyna; Gamian, Andrzej

    2011-05-01

    The objective of the study was to evaluate whether severe sepsis and septic shock are related to alterations in midkine concentrations, to identify disease-related factors associated with these alterations, and to initially appraise whether midkine might serve as a biomarker in sepsis. Prospective observational cross-sectional study with 5-day follow-up. Circulating midkine was measured (enzyme-linked immunosorbent assay) in 38 septic (13 with severe sepsis, 25 with septic shock), 82 active inflammatory bowel disease (IBD) (26 with systemic inflammatory response syndrome [SIRS]) patients, and 87 healthy subjects. Midkine significantly increased along with a sequence: health-inflammation (IBD)-systemic inflammation (IBD-SIRS)-severe sepsis/septic shock. High midkine levels (>1,000 ng/L) were found in 63% of septic and in 19% of IBD-SIRS patients, whereas extremely high concentrations (>5,000 ng/L) were found in 16% vs. 4%. Although not different at admission, midkine gradually decreased in severe sepsis and remained high in shock. Similarly, persistently high midkine was observed in patients with cardiovascular insufficiency (CVI) and in mechanically ventilated as compared with normalizing levels in patients without CVI and not requiring ventilation. The differences in devised simple rates (Δ5th-1st) were significant in all these cases. Accordingly, admission midkine was higher in patients with metabolic acidosis. Concerning pathogen, gram-positive infections were associated with the highest midkine levels. In conclusion, sepsis and septic shock are associated with midkine elevation, substantially more pronounced than in inflammation, even systemic, revealing a new potential mediator of deregulation of neutrophil migration. Sepsis-related global hypoxia seems to contribute to midkine elevation. Our results substantiate further research on possible midkine application as a sepsis biomarker: in differentiating SIRS from sepsis and identifying gram-positive sepsis and

  2. Sepsis in intensive care unit patients with traumatic brain injury: factors associated with higher mortality

    PubMed Central

    Cardozo, Luis Carlos Maia; da Silva, Redson Ruy

    2014-01-01

    Objective Patients with traumatic brain injury are particularly susceptible to sepsis, which may exacerbate the systemic inflammatory response and lead to organ dysfunction. The influence of clinical variables on the mortality of intensive care unit patients with traumatic brain injury and sepsis was investigated. Methods The present investigation was a retrospective study involving 175 patients with traumatic brain injury who were treated in a period of 1 year at a reference hospital for trauma and who had sepsis, severe sepsis, or septic shock. Demographic and clinical data were obtained, and the SOFA score was calculated at the time sepsis was found and after 72 hours. Results There was a predominance of young men with severe traumatic brain injury, multiple head injuries, sepsis with a pulmonary focus, prolonged hospital stay, and high mortality (37.7%). Circulatory and respiratory failure had a high incidence, but renal and coagulation failure were less frequent, and liver failure was not observed. After logistic regression, the presence of septic shock and respiratory failure 72 hours after the sepsis diagnosis was associated with higher mortality, with an odds ratio of 7.56 (95%CI=2.04-27.31, p=0.0024) and 6.62 (95%CI=1.93-22.78, p=0.0027), respectively. In addition, there was a higher mortality among patients who had no organ failure on D1 but who developed the condition after 72 hours of sepsis and in those patients who already had organ failure at the time sepsis was diagnosed and remained in this condition after 72 hours. Conclusion Septic shock and progressive organ (particularly respiratory) dysfunction increases the mortality of patients with traumatic brain injury and sepsis. PMID:25028949

  3. AspiriN To Inhibit SEPSIS (ANTISEPSIS) randomised controlled trial protocol

    PubMed Central

    Eisen, Damon P; Moore, Elizabeth M; Leder, Karin; Lockery, Jessica; McBryde, Emma S; McNeil, John J; Pilcher, David; Wolfe, Rory; Woods, Robyn L

    2017-01-01

    Introduction Sepsis is a leading global cause of morbidity and mortality, and is more common at the extremes of age. Moreover, the cost of in-hospital care for elderly patients with sepsis is significant. There are indications from experimental and observational studies that aspirin may reduce inflammation associated with infection. This paper describes the rationale and design of the AspiriN To Inhibit SEPSIS (ANTISEPSIS) trial, a substudy of ASPirin in Reducing Events in the Elderly (ASPREE). ANTISEPSIS primarily aims to determine whether low-dose aspirin reduces sepsis-related deaths in older people. Additionally, it will assess whether low-dose aspirin reduces sepsis-related hospitalisations and sepsis-related Intensive Care Unit (ICU) admissions. Methods and analysis ASPREE is a double-blinded, randomised, placebo-controlled primary prevention trial that will determine whether daily low-dose aspirin extends disability-free longevity in 19 000 healthy older people recruited in Australia and the USA. The ANTISEPSIS substudy involves additional ASPREE trial data collection to assess the impact of daily low-dose aspirin on sepsis-related events in the 16 703 ASPREE participants aged 70 years and over, recruited in Australia. The intervention is a daily 100 mg dose of enteric-coated aspirin versus matching placebo, with 1:1 randomisation. The primary outcome for the ANTISEPSIS substudy is the incidence of sepsis-related death in eligible patients. The incidence of sepsis-related hospital and ICU admissions are secondary outcomes. ANTISEPSIS is to be conducted between 2012 and 2018. Discussion This substudy will determine whether aspirin, an inexpensive and accessible therapy, safely reduces sepsis-related deaths and hospitalisations in older Australians. If shown to be the case, this would have profound effects on the health of older Australians. Trial registration number Pre-results, ACTRN12613000349741. PMID:28110287

  4. CB2 Cannabinoid Receptors Contribute to Bacterial Invasion and Mortality in Polymicrobial Sepsis

    PubMed Central

    Csóka, Balázs; Németh, Zoltán H.; Mukhopadhyay, Partha; Spolarics, Zoltán; Rajesh, Mohanraj; Federici, Stephanie; Deitch, Edwin A.; Bátkai, Sándor; Pacher, Pál; Haskó, György

    2009-01-01

    Background Sepsis is a major healthcare problem and current estimates suggest that the incidence of sepsis is approximately 750,000 annually. Sepsis is caused by an inability of the immune system to eliminate invading pathogens. It was recently proposed that endogenous mediators produced during sepsis can contribute to the immune dysfunction that is observed in sepsis. Endocannabinoids that are produced excessively in sepsis are potential factors leading to immune dysfunction, because they suppress immune cell function by binding to G-protein-coupled CB2 receptors on immune cells. Here we examined the role of CB2 receptors in regulating the host's response to sepsis. Methods and Findings The role of CB2 receptors was studied by subjecting CB2 receptor wild-type and knockout mice to bacterial sepsis induced by cecal ligation and puncture. We report that CB2 receptor inactivation by knockout decreases sepsis-induced mortality, and bacterial translocation into the bloodstream of septic animals. Furthermore, CB2 receptor inactivation decreases kidney and muscle injury, suppresses splenic nuclear factor (NF)-κB activation, and diminishes the production of IL-10, IL-6 and MIP-2. Finally, CB2 receptor deficiency prevents apoptosis in lymphoid organs and augments the number of CD11b+ and CD19+ cells during CLP. Conclusions Taken together, our results establish for the first time that CB2 receptors are important contributors to septic immune dysfunction and mortality, indicating that CB2 receptors may be therapeutically targeted for the benefit of patients suffering from sepsis. PMID:19641602

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

    PubMed Central

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

    2015-01-01

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

  6. Septris: A Novel, Mobile, Online, Simulation Game That Improves Sepsis Recognition and Management

    PubMed Central

    Daines, William; Tsui, Jamie; Strehlow, Matthew; Maggio, Paul; Shieh, Lisa

    2015-01-01

    Problem Annually affecting over 18 million people worldwide, sepsis is common, deadly, and costly. Despite significant effort by the Surviving Sepsis Campaign and other initiatives, sepsis remains underrecognized and undertreated. Approach Research indicates that educating providers may improve sepsis diagnosis and treatment; thus, the Stanford School of Medicine has developed a mobile-accessible, case-based, online game entitled Septris (http://med.stanford.edu/septris/). Septris, launched online worldwide in December 2011, takes an innovative approach to teaching early sepsis identification and evidence-based management. The free gaming platform leverages the massive expansion over the past decade of smartphones and the popularity of noneducational gaming. The authors sought to assess the game’s dissemination and its impact on learners’ sepsis-related knowledge, skills, and attitudes. In 2012, the authors trained Stanford pregraduate (clerkship) and postgraduate (resident) medical learners (n = 156) in sepsis diagnosis and evidence-based practices via 20 minutes of self-directed game play with Septris. The authors administered pre- and posttests. Outcomes By October 2014, Septris garnered over 61,000 visits worldwide. After playing Septris, both pre- and postgraduate groups improved their knowledge on written testing in recognizing and managing sepsis (P < .001). Retrospective self-reporting on their ability to identify and manage sepsis also improved (P < .001). Over 85% of learners reported that they would or would maybe recommend Septris. Next Steps Future evaluation of Septris should assess its effectiveness among different providers, resource settings, and cultures; generate information about how different learners make clinical decisions; and evaluate the correlation of game scores with sepsis knowledge. PMID:25517703

  7. Epidemiology of systemic inflammatory response syndrome and sepsis in cats hospitalized in a veterinary teaching hospital.

    PubMed

    Babyak, Jonathan M; Sharp, Claire R

    2016-07-01

    OBJECTIVE To describe the epidemiology of the systemic inflammatory response syndrome (SIRS) and sepsis in cats hospitalized in a veterinary teaching hospital. DESIGN Observational study. ANIMALS 246 client-owned cats. PROCEDURES During a 3-month period, daily treatment records were evaluated for all hospitalized cats. Information extracted included signalment, temperature, heart rate, respiratory rate, diagnostic test results, diagnosis, duration of hospitalization, and outcome (survival or death). Cats were classified into 1 of 4 disease categories (sepsis [confirmed infection and SIRS], infection [confirmed infection without SIRS], noninfectious SIRS [SIRS without a confirmed infection], and no SIRS [no SIRS or infection]). RESULTS Of the 246 cats, 26 and 3 were hospitalized 2 and 3 times, respectively; thus, 275 hospitalizations were evaluated. When SIRS was defined as the presence of ≥ 2 of 4 SIRS criteria, 17 cats had sepsis, 16 had infections, 81 had noninfectious SIRS, and 161 were classified in the no SIRS category at hospital admission. The prevalence of sepsis at hospital admission was 6.2 cases/100 admissions. Four cats developed sepsis while hospitalized, resulting in a sepsis incidence rate of 1.5 cases/100 hospital admissions. Four of 17 cats with sepsis at hospital admission and 3 of 4 cats that developed sepsis while hospitalized died or were euthanized, resulting in a mortality rate of 33.3% for septic cats; 239 hospitalizations resulted in survival, 28 resulted in euthanasia, and 8 resulted in death. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that many hospitalized cats have evidence of SIRS and some have sepsis. In cats, sepsis is an important clinical entity with a high mortality rate.

  8. [Myocardial dysfunction in sepsis--definition and pathogenetic mechanisms].

    PubMed

    Muriová, K; Maláska, J; Otevrel, F; Slezák, M; Kratochvíl, M; Sevík, P

    2010-03-01

    Sepsis is considered to be the major cause of morbidity and mortality of patients hospitalised in intensive care. It's defined as a systemic inflammatory response of organism to infection. Incidence of myocardial dysfunction in studies with severe sepsis patients is up to two thirds of patients. Cardiac dysfunction shows a continuum from isolated and mild diastolic dysfunction to combined severe diastolic and systolic failure of both ventricles mimicking even cardiogenic shock in some patients. Typical features of septic myocardial dysfunction (SMD) are decrease in ejection fraction (EF) with dilatation ofventricles, e.g. increase in end-diastolic volume (EDV). Reversibility of myocardial dysfunction during a period from 7 to 10 days in survivors is other typical manifestation of SMD. Hence, one can speculate that development of such a type ofSMD as a temporary protective compensatory mechanism could be advantageous for of an individual patient. A large body ofevidence about mechanisms ofSMD was described; endothelial dysfunction with consequent microcirculatory and mitochondrial dysfunction and role of circulating factors are considered to be the most important.

  9. Endogenous immunoglobulins and sepsis: New perspectives for guiding replacement therapies.

    PubMed

    Bermejo-Martin, Jesús F; Giamarellos-Bourboulis, Evangelos J

    2015-12-01

    The recently emerging concept of immunosuppression developing in the field of severe sepsis generated the need to measure circulating immunoglobulins as part of the necessary tests to evaluate immunocompetence status in patients suffering from this condition. Serum concentrations can be used as a surrogate marker of the final outcome and as a biomarker to explore the need for supplementation of the host with intravenous immunoglobulin preparations. Available evidence from recent clinical studies pinpoints the main observations. The first is that circulating IgM is a phenomenon associated with progression from severe sepsis to septic shock. Deficient kinetics of circulating IgM during the first 7 days following the start of vasopressors is linked with unfavourable outcome. The second is the development of immunoscores using low levels of IgM, IgG1 and IgA. These immunoscores can predict 28-day mortality with an odds ratio ranging between 3 and 5. Novel techniques for evaluating patient's immune status are shedding new light on the development of modern therapeutics where immunoglobulin replacement may be part of a personalised therapeutic approach.

  10. Reprogramming of circulatory cells in sepsis and SIRS.

    PubMed

    Cavaillon, J-M; Adrie, C; Fitting, C; Adib-Conquy, M

    2005-01-01

    Immune status is altered in patients with sepsis or non-infectious systemic inflammatory response syndrome (SIRS). Reduced ex-vivo TNF production by endotoxin-activated monocytes has been regularly reported. This observation is reminiscent of the phenomenon of endotoxin tolerance, and the term 'leukocyte reprogramming' well defines this phenomenon. This review will outline that the hyporesponsiveness of circulating leukocytes is not a generalized phenomenon in sepsis and SIRS. Indeed, the nature of the insult (i.e. infectious versus non-infectious SIRS; under anesthesia [surgery] or not [trauma, burn]), the nature of the activator used to trigger leukocytes (i.e. different Toll-like receptor ligands or whole bacteria), the nature of the cell culture (i.e. isolated monocytes versus peripheral blood mononuclear cells versus whole blood assays), and the nature of the analyzed cytokines (e.g. IL-1beta versus IL-1ra; TNF versus IL-10) have a profound influence on the outcome of the response.

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

    PubMed

    Burdon, Dan; Zabel, Peter

    2002-01-01

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

  12. Inflammatory markers in SIRS, sepsis and septic shock.

    PubMed

    Herzum, I; Renz, H

    2008-01-01

    Despite great advancement in the understanding of the pathophysiology and in the development of novel therapeutic approaches, mortality of sepsis still remains unacceptably high. Adequate laboratory diagnostics represents a major requirement for the improvement of this situation. For a better understanding of the immunological dysregulation in this disease, several markers are now available for routine diagnostics in the clinical laboratory. They include the cytokines interleukin (IL) -6, IL-8, procalcitonin and the LPS-binding protein (LBP). These novel markers will be compared to the conventional procedure of diagnosing inflammatory and infectious disease, such as measurements of C-reactive protein (CRP) as a major acute phase protein and differential blood counting. Important questions addressed in this review are the usefulness of these markers for early diagnosis, their role as prognostic markers and in the risk assessment of patients. Furthermore, we will discuss whether these parameters are to differentiate between systemic inflammatory response syndrome (SIRS) and sepsis at its different degrees. In the case of an infectious nature of the disease, it is important to differentiate between viral or bacterial origin and to monitor the responsiveness of antibiotic therapies. The literature was analysed with focus on the evidence for diagnostic and analytical performance. For this purpose international definition and staging criteria were used in context of criteria for assay performance including sensitivity, specificity, negative and positive predictive values, ROC analysis and other analytical criteria.

  13. Heparin defends against the toxicity of circulating histones in sepsis.

    PubMed

    Wang, Feifei; Zhang, Naipu; Li, Biru; Liu, Lanbo; Ding, Lei; Wang, Ying; Zhu, Yimin; Mo, Xi; Cao, Qing

    2015-06-01

    Although circulating histones were demonstrated as major mediators of death in septic mice models, their roles in septic patients are not clarified. The present study sought to evaluate the clinical relevance of the circulating histone levels in septic children, and the antagonizing effects of heparin on circulating histones. Histone levels in the plasma of septic children were significantly higher than healthy controls, and positively correlated with disease severity. Histone treatment could activate NF-κB pathway of the endothelial cells and induce the secretion of large amount of cytokines that further amplify inflammation, subsequently leading to organ damage. Co-injection of low dose heparin with lethal dose histones could protect mouse from organ damage and death by antagonizing circulating histones, and similar effects were also observed in other septic models. Collectively, these findings indicated that circulating histones might serve as key factors in the pathogenesis of sepsis and their levels in plasma might be a marker for disease progression and prognosis. Furthermore, low dose heparin might be an effective therapy to hamper sepsis progression and reduce the mortality.

  14. Regenerative Engineering and Bionic Limbs

    PubMed Central

    James, Roshan; Laurencin, Cato T.

    2015-01-01

    Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next

  15. Conservative surgical management of necrotic tissues following meningococcal sepsis: case report of a child treated with hyperbaric oxygen.

    PubMed

    Takac, Ines; Kvolik, Slavica; Divkovic, Dalibor; Kalajdzic-Candrlic, Jasenka; Puseljic, Silvija; Izakovic, Senka

    2010-01-01

    This article presents the case of a 5-month-old infant, who survived a fulminant meningococcal sepsis with purpura fulminans, septic shock and severe DIC with gastrointestinal bleeding. Amputation and reconstructive surgery were considered to treat the multiple skin and limb necroses at high risk of superinfection, but the surgical intervention was delayed due to the extremely doubtful outcome. On Day 10 after the onset of the disease, a hemodynamic improvement was achieved. The baby overcame early critical period, but was still in poor general condition. The hyperbaric oxygenation (HBO2) as adjuvant therapy was started in the monoplace chamber using the following protocol: from first through fifth day 45 minutes twice a day on 1.5 atmosphere absolute (ATA); after a two-day break, once a day on 1.8 ATA for 60 minutes. During 52 HBO2 treatments multiple areas of necrotic skin and subcutaneous tissue, together with fingertips and toes, detached spontaneously. All wounds healed without reinfections. An increased oxygen concentration during HBO2 therapy promoted spontaneous wound healing. Bacterial superinfection was not observed in numerous low-perfused lesions. Since repeated anesthesia and surgical interventions were not needed, a final invalidity was minimized. To the best of our knowledge, this is the first report on the successful conservative surgical treatment of this mutilating disease without aggressive reconstructive surgery in an infant with the help of HBO2.

  16. Modulation of Myocardial Mitochondrial Mechanisms during Severe Polymicrobial Sepsis in the Rat

    PubMed Central

    Chopra, Mani; Golden, Honey B.; Mullapudi, Srinivas; Dowhan, William; Dostal, David E.; Sharma, Avadhesh C.

    2011-01-01

    Background We tested the hypothesis that 5-Hydroxydecanoic acid (5HD), a putative mitoKATP channel blocker, will reverse sepsis-induced cardiodynamic and adult rat ventricular myocyte (ARVM) contractile dysfunction, restore mitochondrial membrane permeability alterations and improve survival. Methodology/Principal Findings Male Sprague-Dawley rats (350–400 g) were made septic using 400 mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. The Voltage Dependent Anion Channels (VDAC1), Bax and cytochrome C levels were determined in isolated single ARVMs obtained from sham and septic rat heart. Mitochondria and cytosolic fractions were isolated from ARVMs treated with norepinephrine (NE, 10 µmoles) in the presence/absence of 5HD (100 µmoles). A continuous infusion of 5HD using an Alzet pump reversed sepsis-induced mortality when administered at the time of induction of sepsis (−40%) and at 6 hr post-sepsis (−20%). Electrocardiography revealed that 5HD reversed sepsis-induced decrease in the average ejection fraction, Simpsons+m Mode (53.5±2.5 in sepsis and 69.2±1.2 at 24 hr in sepsis+5HD vs. 79.9±1.5 basal group) and cardiac output (63.3±1.2 mL/min sepsis and 79.3±3.9 mL/min at 24 hr in sepsis+5HD vs. 85.8±1.5 mL/min basal group). The treatment of ARVMs with 5HD also reversed sepsis-induced depressed contractility in both the vehicle and NE-treated groups. Sepsis produced a significant downregulation of VDAC1, and upregulation of Bax levels, along with mitochondrial membrane potential collapse in ARVMs. Pretreatment of septic ARVMs with 5HD blocked a NE-induced decrease in the VDAC1 and release of cytochrome C. Conclusion The data suggest that Bax activation is an upstream event that may precede the opening of the mitoKATP channels in sepsis. We concluded that mitoKATP channel inhibition via decreased mitochondrial membrane potential and reduced release of cytochrome C provided protection against sepsis-induced ARVM and myocardial

  17. Effects of varying inter-limb spacing to limb length ratio in metachronal swimming

    NASA Astrophysics Data System (ADS)

    Lai, Hong Kuan; Merkel, Rachael; Santhanakrishnan, Arvind

    2016-11-01

    Crustaceans such as shrimp, krill and crayfish swim by rhythmic paddling of four to five pairs of closely spaced limbs. Each pair is phase-shifted in time relative to the neighboring pair, resulting in a metachronal wave that travels in the direction of animal motion. The broad goal of this study is to investigate how the mechanical design of the swimming limbs affect scalability of metachronal swimming in terms of limb-based Reynolds number (Re). A scaled robotic model of metachronal paddling was developed, consisting of four pairs of hinged acrylic plates actuated using stepper motors that were immersed in a rectangular tank containing water-glycerin fluid medium. 2D PIV measurements show that the propulsive jets transition from being primarily horizontal (thrust-producing direction) at Re of order 10 to angled vertically at Re of order 100. The ratio of inter-limb spacing to limb length among metachronal swimming organisms ranges between 0.2 to 0.65. 2D PIV will be used to examine the jets generated between adjacent limbs for varying inter-limb spacing to limb length ratios. The effect of increasing this ratio to beyond the biologically observed range will be discussed.

  18. Late-onset sepsis due to Staphylococcus capitis 'neonatalis' in low-birthweight infants: a new entity?

    PubMed

    Ben Said, M; Hays, S; Bonfils, M; Jourdes, E; Rasigade, J-P; Laurent, F; Picaud, J-C

    2016-09-01

    During hospitalization, sepsis occurs in one of every five very-low-birthweight infants. The emergence of Staphylococcus capitis (SC)-related sepsis in preterm infants was observed recently. This study aimed to evaluate the clinical severity of SC-related sepsis in preterm infants. Of the 105 infants who presented with sepsis related to coagulase-negative staphylococci, 74 were SC. Severe morbidity was more common in the SC group (55.4%) than in the non-SC coagulase-negative staphylococci group (32.0%) (P=0.03). Multi-variate analysis identified SC-related sepsis as an independent risk factor for severe morbidity.

  19. Controversies in sepsis clinical trials: proceedings of a meeting of the International Sepsis Forum, Lausanne, Switzerland, September 29, 2001.

    PubMed

    Dellinger, R Phillip; Abraham, Edward; Bernard, Gordon; Marshall, John C; Vincent, Jean-Louis

    2006-03-01

    Despite some recent success with clinical trials studying innovative therapies in sepsis, the field remains predominantly one of failure despite compounds with significant preclinical activity. Preclinical animal experimentation remains an important component of drug development, and a portfolio approach is recommended. Failure in animals is more likely to predict failure in humans; however, success in animals often does not predict success in humans. Because the signal with innovative therapy of sepsis is likely to be low, an oncology model clinical trial approach, in which studies start with a high-risk homogeneous population and look for a large treatment effect with smaller numbers of patients, is likely to be more relevant than the commonly used cardiology model, in which studies search for a small treatment effect using large, heterogeneous, low-risk populations. With certain rules in place, improvement in organ function may be a worthwhile alternative to mortality as a clinical end point. Once a therapy is approved, adopting less stringent but still appropriate criteria for the use of that therapy in clinical practice may be appropriate.

  20. Comparative Assessment of Cytokine Pattern in Early and Late Onset of Neonatal Sepsis

    PubMed Central

    Khaertynov, Kh. S.; Andreeva, A. A.; Satrutdinov, M. A.; Agafonova, E. A.

    2017-01-01

    Neonatal sepsis is a significant health issue associated with high mortality. Immune responses associated with neonatal sepsis, such as proinflammatory cytokine production, are believed to play a central role in the pathogenesis of this disease. In the present study, serum levels of the proinflammatory cytokines TNF-α, IL1-β, and IL-6 and the anti-inflammatory cytokines IL-4 and IL-10 were evaluated for 25 subjects with neonatal sepsis. We observed that subjects with late onset of sepsis (LOS), as well as those with early onset of sepsis (EOS), had a substantial increase in serum TNF-α. In contrast to EOS, subjects with LOS demonstrated a significant increase in serum levels IL-6 and IL-10. Additionally, we observed a significant difference in cytokine profiles between acute and postacute cases of neonatal sepsis. For instance, the level of proinflammatory cytokines, such as TNF-α and IL-6, was elevated in the acute phase, whereas the production of anti-inflammatory cytokines, such as IL-10, became substantially upregulated during the postacute phase. Additionally, no correlation was observed between cytokine levels and CRP levels or lymphocyte counts. Thus, in contrast to CRP levels and lymphocyte counts, examination of the cytokine profile can provide valuable information when determining the most effective therapy for treating neonatal sepsis. This information may be useful to physicians when determining if anti-inflammatory or immune stimulatory therapy is warranted. PMID:28367457

  1. Escherichia coli counting using lens-free imaging for sepsis diagnosis

    NASA Astrophysics Data System (ADS)

    Moon, Sangjun; Manzur, Fahim; Manzur, Tariq; Klapperich, Catherine; Demirci, Utkan

    2009-09-01

    Sepsis causes 9.3% of overall deaths in United States. To diagnose sepsis, cell/bacteria capture and culturing methods have been widely investigated in the medical field. Escherichia Coli (E. Coli) is used as a model organism for sepsis in blood stream since wide variety of antibodies are established and the genetic modification process is well documented for fluorescent tagging. In point-of-care testing applications, the sepsis diagnostics require fast monitoring, inexpensive testing, and reliable results at resource limited settings, i.e. battle field, home care for dialysis. However, the cell/E.coli are hard to directly capture and see at the POCT because of the small size, 2 μm long and 0.5 μm in diameter, and the bacteria are rare in the blood stream in sepsis. Here, we propose a novel POCT platform to image and enumerate cell/E.coli on a microfluidic surface to diagnose sepsis at resource limited conditions. We demonstrate that target cells are captured from 5 μl of whole blood using specific antibodies and E.coli are imaged using a lens-free imaging platform, 2.2 μm pixel CMOS based imaging sensor. This POCT cell/bacteria capture and enumeration approach can further be used for medical diagnostics of sepsis. We also show approaches to rapidly quantify white blood cell counts from blood which can be used to monitor immune response.

  2. Determinants of Carboxyhemoglobin Levels and Relationship with Sepsis in a Retrospective Cohort of Preterm Neonates

    PubMed Central

    Sim, Kathleen; Parrish, Graham; Hoggart, Clive; Wang, Yifei; Kroll, J. Simon; Godambe, Sunit

    2016-01-01

    Carboxyhemoglobin levels in blood reflect endogenous carbon monoxide production and are often measured during routine blood gas analysis. Endogenous carbon monoxide production has been reported to be increased during sepsis, but carboxyhemoglobin levels have not been thoroughly evaluated as a biomarker of sepsis. We sought to determine whether carboxyhemoglobin levels were elevated during sepsis in a high risk population of premature neonates. We conducted a retrospective cohort study of 30 infants in two neonatal intensive care units using electronic medical and laboratory records. The majority of infants were extremely premature and extremely low birth weight, and 25 had at least one episode of sepsis. We collected all carboxyhemoglobin measurements during their in-patient stay and examined the relationship between carboxyhemoglobin and a variety of clinical and laboratory parameters, in addition to the presence or absence of sepsis, using linear mixed-effect models. We found that postnatal age had the most significant effect on carboxyhemoglobin levels, and other significant associations were identified with gestational age, hemoglobin concentration, oxyhemoglobin saturation, and blood pH. Accounting for these covariates, there was no significant relationship between the onset of sepsis and carboxyhemoglobin levels. Our results show that carboxyhemoglobin is unlikely to be a clinically useful biomarker of sepsis in premature infants, and raise a note of caution about factors which may confound the use of carbon monoxide as a clinical biomarker for other disease processes such as hemolysis. PMID:27552216

  3. Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS.

    PubMed

    Kangelaris, Kirsten Neudoerffer; Prakash, Arun; Liu, Kathleen D; Aouizerat, Bradley; Woodruff, Prescott G; Erle, David J; Rogers, Angela; Seeley, Eric J; Chu, Jeffrey; Liu, Tom; Osterberg-Deiss, Thomas; Zhuo, Hanjing; Matthay, Michael A; Calfee, Carolyn S

    2015-06-01

    The early sequence of events leading to the development of the acute respiratory distress syndrome (ARDS) in patients with sepsis remains inadequately understood. The purpose of this study was to identify changes in gene expression early in the course of illness, when mechanisms of injury may provide the most relevant treatment and prognostic targets. We collected whole blood RNA in critically ill patients admitted from the Emergency Department to the intensive care unit within 24 h of admission at a tertiary care center. Whole genome expression was compared in patients with sepsis and ARDS to patients with sepsis alone. We selected genes with >1 log2 fold change and false discovery rate <0.25, determined their significance in the literature, and performed pathway analysis. Several genes were upregulated in 29 patients with sepsis with ARDS compared with 28 patients with sepsis alone. The most differentially expressed genes included key mediators of the initial neutrophil response to infection: olfactomedin 4, lipocalin 2, CD24, and bactericidal/permeability-increasing protein. These gene expression differences withstood adjustment for age, sex, study batch, white blood cell count, and presence of pneumonia or aspiration. Pathway analysis demonstrated overrepresentation of genes involved in known respiratory and infection pathways. These data indicate that several neutrophil-related pathways may be involved in the early pathogenesis of sepsis-related ARDS. In addition, identifiable gene expression differences occurring early in the course of sepsis-related ARDS may further elucidate understanding of the neutrophil-related mechanisms in progression to ARDS.

  4. A Pathophysiological Insight into Sepsis and Its Correlation with Postmortem Diagnosis

    PubMed Central

    Pomara, C.; Riezzo, I.; Bello, S.; De Carlo, D.; Neri, M.; Turillazzi, E.

    2016-01-01

    Background. Sepsis is among the leading causes of death worldwide and is the focus of a great deal of attention from policymakers and caregivers. However, sepsis poses significant challenges from a clinical point of view regarding its early detection and the best organization of sepsis care. Furthermore, we do not yet have reliable tools for measuring the incidence of sepsis. Methods based on analyses of insurance claims are unreliable, and postmortem diagnosis is still challenging since autopsy findings are often nonspecific. Aim. The objective of this review is to assess the state of our knowledge of the molecular and biohumoral mechanisms of sepsis and to correlate them with our postmortem diagnosis ability. Conclusion. The diagnosis of sepsis-related deaths is an illustrative example of the reciprocal value of autopsy both for clinicians and for pathologists. A complete methodological approach, integrating clinical data by means of autopsy and histological and laboratory findings aiming to identify and demonstrate the host response to infectious insults, is mandatory to illuminate the exact cause of death. This would help clinicians to compare pre- and postmortem findings and to reliably measure the incidence of sepsis. PMID:27239102

  5. Diagnostic utility of biomarkers for neonatal sepsis--a systematic review.

    PubMed

    Hedegaard, Sofie Sommer; Wisborg, Kirsten; Hvas, Anne-Mette

    2015-03-01

    Neonatal sepsis is a major cause of morbidity and mortality. Early diagnosis and treatment of the neonate with suspected sepsis are essential to prevent life-threatening complications. Diagnosis of neonatal sepsis is a challenge due to non-specific clinical signs and the fact that infection markers are difficult to interpret in the first and critical phase of neonatal sepsis. The objective of the present study was to systematically evaluate existing evidence of the diagnostic utility of biomarkers for prediction of sepsis in neonates. We conducted a systematic literature search performed in PubMed and Embase. The study population was neonates with gestation age > 24 weeks in their first 28 days of life with suspected sepsis. The included manuscripts were rated due to criteria from a modified rating scale developed by Douglas Altman. Of 292 potentially relevant manuscripts, 77 fulfilled the inclusion and exclusion criteria; 16 (21%) were rated as high-quality studies. C-reactive protein (CRP) was the most extensively studied biomarker evaluated. The high-quality studies indicated that the acute phase protein serum amyloid A had high sensitivity, both at onset of symptoms and 2 days after. The studies evaluating serum amyloid A presented a variable positive predictive value (PPV, 0.67 and 0.92) with a high negative predictive value (NPV, 0.97 and 1.00). The existing evidence of the diagnostic value of serum amyloid A for neonatal sepsis showed promising results, and should be further investigated in clinical settings.

  6. The use of common continuous monitoring parameters: a quality indicator for critically ill patients with sepsis.

    PubMed

    Giuliano, Karen K; Kleinpell, Ruth

    2005-01-01

    Sepsis is a common source of morbidity and mortality among critically ill patients, and targeting measures to promote early recognition and treatment of sepsis is at the forefront of many critical care initiatives. Starting formally in 1992, with the publication of the definitions of sepsis, continuous monitoring of several common physiologic parameters, including electrocardiogram, blood pressure, and oxygen saturation, have been advocated as important in the early identification and treatment of patients with sepsis. The descriptive study detailed in this article was conducted to assess the perceptions and clinical continuous physiologic monitoring practices of experienced critical care clinicians with regard to their use of common physiologic monitoring parameters in the care of patients with sepsis. A convenience sample of 100 physicians and 517 nurses completed a 20-item survey assessing perceptions and clinical monitoring practices related to the care of patients with sepsis. Results indicated that the basic parameters of electrocardiogram, invasive blood pressure, pulmonary arterial catheter monitoring, and oxygen saturation all have value in the recognition and treatment of patients with sepsis. The majority of clinicians used these parameters routinely and felt they were necessary for patient care. These results indicate that clinical practice is in concordance with current practice recommendations.

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

    PubMed Central

    Zhu, Yanping; Fu, Yanxia; Lin, Hairong

    2016-01-01

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

  8. The changing immune system in sepsis: is individualized immuno-modulatory therapy the answer?

    PubMed

    Boomer, Jonathan S; Green, Jonathan M; Hotchkiss, Richard S

    2014-01-01

    Sepsis remains the leading cause of death in most intensive care units. Advances in understanding the immune response to sepsis provide the opportunity to develop more effective therapies. The immune response in sepsis can be characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immune-suppressive phase. Patients fail to eradicate invading pathogens and are susceptible to opportunistic organisms in the hypo-inflammatory phase. Many mechanisms are responsible for sepsis-induced immuno-suppression, including apoptotic depletion of immune cells, increased T regulatory and myeloid-derived suppressor cells, and cellular exhaustion. Currently in clinical trial for sepsis are granulocyte macrophage colony stimulating factor and interferon gamma, immune-therapeutic agents that boost patient immunity. Immuno-adjuvants with promise in clinically relevant animal models of sepsis include anti-programmed cell death-1 and interleukin-7. The future of immune therapy in sepsis will necessitate identification of the immunologic phase using clinical and laboratory parameters as well as biomarkers of innate and adaptive immunity.

  9. Functional analysis of eicosanoids from white blood cells in sepsis and SIRS.

    PubMed

    Baenkler, M; Leykauf, M; John, S

    2006-12-01

    Sepsis and SIRS are affections with major alterations in inflammatory activity. The impact of prostaglandins (PG) and leukotrienes (LT) produced from white blood cells (WBC) in this context is not completely understood. Thirty nine patients with sepsis or SIRS were investigated in comparison to 10 healthy controls. WBC were collected and separately exposed to arachidonic acid (AA) or to nothing else. After centrifugation, the generated PGE(2) and LTCDE(4) with or without stimulation were measured in the supernatant. LT-levels were significantly higher during sepsis/SIRS than in controls whereas PG-levels of patients were decreased to those of controls in basic condition. The relation between the level with and without stimulation showed a significant higher ratio in PG in contrast to LTs. The survivor's ratio in LT levels was significantly higher than that of non-survivors, which did not differ from controls. Generation of LT from WBC is enhanced during sepsis/SIRS, but LT generation after stimulation only in survivors but not in non-survivors. This inability of WBC to generate LT during sepsis in non-survivors could be predictive regarding the outcome of sepsis/SIRS and may be part of the "immunoparalysis" seen during sepsis in association with bad outcome.

  10. The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats

    PubMed Central

    Li, Guofu; Jia, Jia; Ji, Kaiqiang; Gong, Xiaoying; Wang, Rui; Zhang, Xiaoli; Wang, Haiyuan; Zang, Bin

    2016-01-01

    Sepsis-induced acute kidney injury (AKI) represents a major cause of mortality in intensive care units. Sivelestat, a selective inhibitor of neutrophil elastase (NE), can attenuate sepsis-related acute lung injury. However, whether sivelestat can preserve kidney function during sepsis remains unclear. In this study, we thus examined the effects of sivelestat on sepsis-related AKI. Cecal ligation and puncture (CLP) was performed to induce multiple bacterial infection in male Sprague-Dawley rats, and subsequently, 50 or 100 mg/kg sivelestat were administered by intraperitoneal injection immediately after the surgical procedure. In the untreated rats with sepsis, the mean arterial pressure (MAP) and glomerular filtration rate (GFR) were decreased, whereas serum blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) levels were increased. We found that sivelestat promoted the survival of the rats with sepsis, restored the impairment of MAP and GFR, and inhibited the increased BUN and NGAL levels; specifically, the higher dose was more effective. In addition, sivelestat suppressed the CLP-induced macrophage infiltration, the overproduction of pro-inflammatory mediators (tumor necrosis factor-α, interleukin-1β, high-mobility group box 1 and inducible nitric oxide synthase) and serine/threonine kinase (Akt) pathway activation in the rats. Collectively, our data suggest that the inhibition of NE activity with the inhibitor, sivelestat, is beneficial in ameliorating sepsis-related kidney injury. PMID:27430552

  11. The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats.

    PubMed

    Li, Guofu; Jia, Jia; Ji, Kaiqiang; Gong, Xiaoying; Wang, Rui; Zhang, Xiaoli; Wang, Haiyuan; Zang, Bin

    2016-09-01

    Sepsis-induced acute kidney injury (AKI) represents a major cause of mortality in intensive care units. Sivelestat, a selective inhibitor of neutrophil elastase (NE), can attenuate sepsis-related acute lung injury. However, whether sivelestat can preserve kidney function during sepsis remains unclear. In this study, we thus examined the effects of sivelestat on sepsis-related AKI. Cecal ligation and puncture (CLP) was performed to induce multiple bacterial infection in male Sprague-Dawley rats, and subsequently, 50 or 100 mg/kg sivelestat were administered by intraperitoneal injection immediately after the surgical procedure. In the untreated rats with sepsis, the mean arterial pressure (MAP) and glomerular filtration rate (GFR) were decreased, whereas serum blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) levels were increased. We found that sivelestat promoted the survival of the rats with sepsis, restored the impairment of MAP and GFR, and inhibited the increased BUN and NGAL levels; specifically, the higher dose was more effective. In addition, sivelestat suppressed the CLP-induced macrophage infiltration, the overproduction of pro-inflammatory mediators (tumor necrosis factor‑α, interleukin-1β, high-mobility group box 1 and inducible nitric oxide synthase) and serine/threonine kinase (Akt) pathway activation in the rats. Collectively, our data suggest that the inhibition of NE activity with the inhibitor, sivelestat, is beneficial in ameliorating sepsis-related kidney injury.

  12. Automated Detection of Sepsis Using Electronic Medical Record Data: A Systematic Review.

    PubMed

    Despins, Laurel A

    2016-09-13

    Severe sepsis and septic shock are global issues with high mortality rates. Early recognition and intervention are essential to optimize patient outcomes. Automated detection using electronic medical record (EMR) data can assist this process. This review describes automated sepsis detection using EMR data. PubMed retrieved publications between January 1, 2005 and January 31, 2015. Thirteen studies met study criteria: described an automated detection approach with the potential to detect sepsis or sepsis-related deterioration in real or near-real time; focused on emergency department and hospitalized neonatal, pediatric, or adult patients; and provided performance measures or results indicating the impact of automated sepsis detection. Detection algorithms incorporated systemic inflammatory response and organ dysfunction criteria. Systems in nine studies generated study or care team alerts. Care team alerts did not consistently lead to earlier interventions. Earlier interventions did not consistently translate to improved patient outcomes. Performance measures were inconsistent. Automated sepsis detection is potentially a means to enable early sepsis-related therapy but current performance variability highlights the need for further research.

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

    PubMed

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

    2015-10-23

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

  14. Emodin alleviates jejunum injury in rats with sepsis by inhibiting inflammation response.

    PubMed

    Chen, Yi-Kun; Xu, Ying-Kun; Zhang, Hao; Yin, Jiang-Tao; Fan, Xin; Liu, Da-Dong; Fu, Hai-Yan; Wan, Bing

    2016-12-01

    Emodin is an anthraquinone derived from Chinese herb that exerts anti-inflammation effects. This study aimed to investigate whether emodin provides the protection for jejunum injury by inhibiting inflammation. We established a model of sepsis caused by cecal ligation and puncture. Forty-eight male Wistar rats were divided into four groups (n=12). Jejunum injury was assessed by pathological examination. The activity of pJAK1/pSTAT3 and protein levels of Bcl-2 and Bax were detected by Western blot analysis. Inflammatory factors IL-6, TNF-α and procalcitonin were detected by ELISA. Apoptosis was detected by TUNEL. We found that emodin alleviated jejunum damage and apoptosis induced by sepsis and decreased the levels of IL-6, TNF-α and procalcitonin in septic rats. Furthermore, we observed that emodin increased the levels of pJAK1 and of pSTAT3, which were decreased in rats with sepsis. In addition, emodin enhanced the expression of Bcl-2 which was downregulated by sepsis and decreased the expression of Bax which was upregulated by sepsis. In conclusion, these results indicate that emodin suppresses inflammatory response induced by sepsis. Emodin activates JAK1/STAT3 signaling pathway and regulates Bcl-2 and Bax expression to protect the jejunum in rats with sepsis.

  15. Maternal Deaths Due to Sepsis in the State of Michigan, 1999–2006

    PubMed Central

    Bauer, Melissa E.; Lorenz, Robert P.; Bauer, Samuel T.; Rao, Krishna; Anderson, Frank W.J.

    2015-01-01

    Objective To identify maternal deaths due to sepsis in the state of Michigan, review the events leading to diagnosis, and evaluate treatment to identify areas for improvement. Methods A case series was collected for maternal deaths due to sepsis from a cohort of maternal deaths in the state of Michigan. The study period was 1999–2006 and included deaths during pregnancy and up to 42 days postpartum. Cases were identified using Maternal Mortality Surveillance records from the Michigan Department of Community Health. Each case was reviewed by all authors. Results Maternal sepsis was the cause of death in 14.6% (22/151) of pregnancy-related deaths. Of 22 deaths, 13 women presented to the hospital with sepsis, two developed sepsis during hospitalization, and seven developed sepsis at home without admission to the hospital for care. Review of available hospital records (n=15) revealed delays in initial appropriate antibiotic treatment occurred in 73% (11/15) of patients. Delay in escalation of care also occurred and was identified in 53% (8/15) of patients. Conclusion Common elements in these deaths illustrate three key delays that may have contributed to the deaths: in recognition of sepsis, in administration of appropriate antibiotics, and in escalation of care. PMID:26348189

  16. Insights into sepsis therapeutic design based on the apoptotic death pathway.

    PubMed

    Hattori, Yuichi; Takano, Ken-ichi; Teramae, Hiroki; Yamamoto, Seiji; Yokoo, Hiroki; Matsuda, Naoyuki

    2010-01-01

    Sepsis remains the leading cause of death in critically ill patients. A major problem contributing to sepsis-related high mortality is the lack of effective medical treatment. Thus, the key goal in critical care medicine is to develop novel therapeutic strategies that will impact favorably on septic patient outcome. While it is generally accepted that sepsis is an inflammatory state resulting from the systemic response to infection, apoptosis is implicated to be an important mechanism of the death of lymphocytes, gastrointestinal and lung epithelial cells, and vascular endothelial cells associated with the development of multiple organ failure in sepsis. The pivotal role of cell apoptosis is now highlighted by multiple studies demonstrating that prevention of cell apoptosis can improve survival in clinically relevant animal models of sepsis. In this review article, we address the scientific rationale for remedying apoptotic cell death in sepsis and propose that therapeutic efforts aimed at blocking cell signaling pathways leading to apoptosis may represent an attractive target for sepsis therapy.

  17. Targeting IL-17A attenuates neonatal sepsis mortality induced by IL-18.

    PubMed

    Wynn, James Lawrence; Wilson, Chris S; Hawiger, Jacek; Scumpia, Philip O; Marshall, Andrew F; Liu, Jin-Hua; Zharkikh, Irina; Wong, Hector R; Lahni, Patrick; Benjamin, John T; Plosa, Erin J; Weitkamp, Jörn-Hendrik; Sherwood, Edward R; Moldawer, Lyle L; Ungaro, Ricardo; Baker, Henry V; Lopez, M Cecilia; McElroy, Steven J; Colliou, Natacha; Mohamadzadeh, Mansour; Moore, Daniel Jensen

    2016-05-10

    Interleukin (IL)-18 is an important effector of innate and adaptive immunity, but its expression must also be tightly regulated because it can potentiate lethal systemic inflammation and death. Healthy and septic human neonates demonstrate elevated serum concentrations of IL-18 compared with adults. Thus, we determined the contribution of IL-18 to lethality and its mechanism in a murine model of neonatal sepsis. We find that IL-18-null neonatal mice are highly protected from polymicrobial sepsis, whereas replenishing IL-18 increased lethality to sepsis or endotoxemia. Increased lethality depended on IL-1 receptor 1 (IL-1R1) signaling but not adaptive immunity. In genome-wide analyses of blood mRNA from septic human neonates, expression of the IL-17 receptor emerged as a critical regulatory node. Indeed, IL-18 administration in sepsis increased IL-17A production by murine intestinal γδT cells as well as Ly6G(+) myeloid cells, and blocking IL-17A reduced IL-18-potentiated mortality to both neonatal sepsis and endotoxemia. We conclude that IL-17A is a previously unrecognized effector of IL-18-mediated injury in neonatal sepsis and that disruption of the deleterious and tissue-destructive IL-18/IL-1/IL-17A axis represents a novel therapeutic approach to improve outcomes for human neonates with sepsis.

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

    PubMed

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

    2016-11-01

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

  19. Human monocytes undergo functional re-programming during sepsis mediated by hypoxia-inducible factor-1α.

    PubMed

    Shalova, Irina N; Lim, Jyue Yuan; Chittezhath, Manesh; Zinkernagel, Annelies S; Beasley, Federico; Hernández-Jiménez, Enrique; Toledano, Victor; Cubillos-Zapata, Carolina; Rapisarda, Annamaria; Chen, Jinmiao; Duan, Kaibo; Yang, Henry; Poidinger, Michael; Melillo, Giovanni; Nizet, Victor; Arnalich, Francisco; López-Collazo, Eduardo; Biswas, Subhra K

    2015-03-17

    Sepsis is characterized by a dysregulated inflammatory response to infection. Despite studies in mice, the cellular and molecular basis of human sepsis remains unclear and effective therapies are lacking. Blood monocytes serve as the first line of host defense and are equipped to recognize and respond to infection by triggering an immune-inflammatory response. However, the response of these cells in human sepsis and their contribution to sepsis pathogenesis is poorly understood. To investigate this, we performed a transcriptomic, functional, and mechanistic analysis of blood monocytes from patients during sepsis and after recovery. Our results revealed the functional plasticity of monocytes during human sepsis, wherein they transited from a pro-inflammatory to an immunosuppressive phenotype, while enhancing protective functions like phagocytosis, anti-microbial activity, and tissue remodeling. Mechanistically, hypoxia inducible factor-1α (HIF1α) mediated this functional re-programming of monocytes, revealing a potential mechanism for their therapeutic targeting to regulate human sepsis.

  20. Running With an Elastic Lower Limb Exoskeleton.

    PubMed

    Cherry, Michael S; Kota, Sridhar; Young, Aaron; Ferris, Daniel P

    2016-06-01

    Although there have been many lower limb robotic exoskeletons that have been tested for human walking, few devices have been tested for assisting running. It is possible that a pseudo-passive elastic exoskeleton could benefit human running without the addition of electrical motors due to the spring-like behavior of the human leg. We developed an elastic lower limb exoskeleton that added stiffness in parallel with the entire lower limb. Six healthy, young subjects ran on a treadmill at 2.3 m/s with and without the exoskeleton. Although the exoskeleton was designed to provide ~50% of normal leg stiffness during running, it only provided 24% of leg stiffness during testing. The difference in added leg stiffness was primarily due to soft tissue compression and harness compliance decreasing exoskeleton displacement during stance. As a result, the exoskeleton only supported about 7% of the peak vertical ground reaction force. There was a significant increase in metabolic cost when running with the exoskeleton compared with running without the exoskeleton (ANOVA, P < .01). We conclude that 2 major roadblocks to designing successful lower limb robotic exoskeletons for human running are human-machine interface compliance and the extra lower limb inertia from the exoskeleton.