Active clinical trials for "Sepsis"

Septic shock is a major cause of morbidity and mortality. SIRS (systemic inflammatory response syndrome) can progress over hours to days to severe sepsis and septic shock. Currently, lactate levels are used to guide resuscitative efforts and have been shown to be a predictor of mortality independent of vital sign abnormalities (1). However, their use seems to be limited to trending in a given patient, and not for prognostic value of a single level (2). This is because there is significant overlap in lactate levels of individuals who progress to death and multisystem organ failure as compared to those who do not (2). Blood cultures are also extensively used to detect blood stream infection (BSI), but these are time consuming and are not immediately useful to clinicians caring for sick patients. A biomarker that adequately distinguishes between patients at high risk for progression to severe sepsis/shock/death and those who will not would be helpful in the appropriate initiation of aggressive treatment and appropriate disposition of patients in clinical care. Previously, the investigators demonstrated that sPLA2-IIA detected by ELISA assay had a sensitivity of 87% and a specificity of 91% in detecting sepsis (3). Zeus Pharmaceuticals has developed a bedside point-of-care test measuring sPLA2-IIA in real time. The investigators propose to study this assay in terms of its discriminatory value in distinguishing between SIRS from non-infectious causes, sepsis, severe sepsis, and septic shock in a cohort of patients presenting to the emergency department at Anderson and Bethlehem campuses. The investigators propose to better define the threshold level for this marker assay as well as seek to establish its utility in a clinical population. The investigators will take samples of blood from emergency department patients presenting who meet SIRS criteria or have a positive q-SOFA screen. The investigators will take subsequent samples of blood when lactate levels are redrawn as per St. Luke's sepsis protocol. After informed consent is obtained, blood specimens will be run in analyzer provided by Zeus for sPLA2-IIA. The investigators will record presence and quantity of sPLA2-IIA, as well as other markers of sepsis such as lactate, vital signs, blood cultures, and patient oriented outcomes (ie ICU days, organ dysfunction, and survival to discharge). Printouts from analyzer will be stored in locked cabinet, and remaining blood will be discarded. The data will then be compiled by the investigators at St. Luke's University Hospital. The results will be correlated with the patients' clinical progression to determine the biomarker's utility and cut-off values for predicting progression of SIRS. As clear threshold levels for this marker have yet to be defined, the investigators would like to enroll patients meeting criteria until the investigators have enrolled 50 patients with septic shock. It is anticipated that, proportionally, this will lead to enrollment of 75-100 patients with severe sepsis, 100-150 patients with sepsis, and 100-150 patients meeting SIRS criteria who are not septic. This will help delineate if there is any value in this assay for distinguishing among the severity of sepsis pathophysiology.

Sepsis is an acute pathology defined as an inappropriate response of the host to infection, resulting in the onset of organ failure (Quick SOFA ≥2, or SOFA ≥2). Septic shock is a sepsis associated with an elevation of lactate ≥ 2 mmol / l and an arterial hypotension requiring vasoactive drugs. Several studies highlighted that sepsis is associated with a plasma L-arginine deficiency. This deficiency induces a lower availability of L-arginine for multiple metabolic pathways including those involved in the synthesis of nitric oxide (NO) in the vascular endothelium via NO synthase. NO is the main endogenous vasodilator mediator, a lower synthesis induces a vascular and endothelial dysfunction that can promote the occurrence of an organic dysfunction during sepsis. Decrease in available NO was confirmed in patients with sepsis and appears correlated with severity. L-arginine deficiency can have multiple origins: L-arginine deficiency resulting from a decrease in endogenous production from citrulline synthesized by the enterocytes. Such enterocyte dysfunction has been confirmed in patients with sepsis and is characterized biologically by elevated plasma levels of I-FABP (intestinal fatty acid binding protein - enterocyte-specific protein, cytolysis marker) and lower than that of citrulline (hypocitrullinemia, marker of lower activity). L-arginine deficiency may also result from a catabolism increase via arginase activity increased. This ubiquitous enzyme, having 2 isoforms (Arg1 and Arg2), allows the synthesis of urea and ornithine from L-arginine. An increase in arginase activity would decrease the available reserves of L-arginine for NO synthesis. The objectives of this work is to evaluate, in patients with severe sepsis or septic shock, the prognostic value of the plasma arginase activity and the plasma expression of 2 isoforms Arg1 and Arg2, their kinetics, and the link between activity / expression of arginase and enterocyte dysfunction.

In this observational study, it is aimed to investigate the mortality and morbidity rates of hospital-acquired blood stream infections that are treated in intensive care units (ICU). The effects of properties of the micro-organism such as type and antimicrobial resistance on the infection and its outcomes will be mainly explored. In addition, the impact of antibiotic options and other treatment modalities on survival of patients will be investigated. Twenty-seven different ICUs from Turkey will be included in this study.

The aim of the current study is to demonstrate dysregulation of immune system΄s circadian rhythms as a consequence of sepsis, as well as marked malfunction of the central circadian clock in comparison with patients without sepsis , the presence of which burdens independently the final outcome and , hence, need to be addressed.

A prospective observational cohort study investigating physiological parameters vs biological markers of whole blood in septic and non-septic pregnant woman to predict systemic immune health

Cardiogenic shock is a condition of low cardiac output that represents the end of a progressive deterioration of cardiac function. The main cause is ischemic heart disease but there are several causes of non-ischemic nature including sepsis. Sepsis is characterized by a picture of organ dysfunction caused by an altered response of the body to an infection. Its most serious form is septic shock, defined as a picture of sepsis in which the underlying abnormalities in the cardiovascular system and cellular metabolism are such as to increase mortality. An organ failure correlates directly with the function of others and this interdependence is especially evident when a cardiovascular failure is established. 3 Cardiac dysfunction in sepsis can be defined as that of a syndrome characterized by low cardiac output not related to myocardial ischemia. The use of levosimendan in cardiogenic shock during sepsis was first described in a 2005 case report. Since then there have been small studies and other case reports that have shown improvements in right and left ventricular contractility, ventricular coupling, cardiopulmonary performance, global oxygen transport, renal and splanchnic perfusion when compared to dobutamine and placebo. Other beneficial effects of this drug have emerged, including an anti-inflammatory, antioxidant and antiapoptotic action with a possible protection from ischemia-reperfusion damage. The present study aims to evaluate the correct use of levosimendan, after the occurrence of cardiogenic shock on a low cardiac index has been ascertained, with the aim of weaning from inotropic drugs in infusion.

There is no consensus around the world on the treatment of preterm rupture of membranes, which is one of the important causes of early neonatal sepsis and one of the common causes of prematurity. Different countries, hospitals and physicians can determine different treatment approaches. There is very little scientific data on the benefit of commonly used treatment regimens other than experience. In this study, scientific results will be obtained by comparing the efficacy of treatments (Sulbactam ampicillin or azithromycin ampicillin) in two different hospitals (Hacettepe University Perinatology Clinic and Ankara City Hospital Perinatology Clinic), and it will be shown which treatment regimen reduces early neonatal sepsis and inflammation better. Some samples (vaginal IL-6, vaginal-cervical swab samples for atypical bacteria, cervical swab samples for direct microscopy, serum IL-6) will be taken from pregnant women who develop membrane rupture and these samples will be used as initial inflammation markers. Each physician will decide on the treatment of his own patient, there will be no intervention in the treatment of the patient within the scope of the research. Patients will continue their routine follow-up after receiving their treatment. When the delivery occurs, the level of IL-6 in the cord blood will be examined with other inflammation markers (procalcitonin, crp, complete blood count), and the neonatal inflammation status of the baby will be determined. The low inflammation markers detected in the babies of pregnant women with high initial inflammation values will be compared and it will be determined which treatment is more effective. At the same time, routine neonatal intensive care follow-ups of these babies will be continued and treatment efficiency in terms of early neonatal sepsis will be determined. This study will present scientific data on which treatment is effective in the literature and will guide international treatment guidelines. At the same time, preterm rupture of membranes will show which bacterial agent plays a more role in the etiology and which of the inflammation markers have more sensitivity and specificity, as well as the success of the treatment, which is the subject of the study. The routine use of some examinations (such as cervical PCR) performed before the treatment begins, is a guide in the selection of agent-specific treatment and may shorten the unnecessary drug use and hospital stay; The management of patients may vary according to the initial inflammation parameters. Physicians evaluating the results of this study can evaluate the risk of their babies in terms of early neonatal sepsis according to the initial inflammation values of their patients, and increase and decrease the length of hospital stay.

After stimulation by lipopolysaccharide (LPS), the one-carbon metabolism of macrophages was significantly up-regulated, the expression of key enzyme 5,10-methylenetetrahydrofolate reductase increased. In vitro experiments we found that LPS stimulation can increase the expression of MTHFR mRNA and protein in macrophages, suggesting that aerobic glycolysis may trigger cytokine storm through one-carbon metabolism. Homocysteine (homocysteine, Hcy) is an important intermediate product of one-carbon metabolism. A number of studies have shown that Hcy is positively correlated with the level of pro-inflammatory factors, significantly enhancing cytokine storm. However, the relationship between Hcy and serum pro-inflammatory factors in patients with sepsis and the effect of Hcy on the prognosis of patients with sepsis are still unclear. Based on the previous work, our research group intends to carry out single-center, prospective, observational clinical research to observe the relationship between homocysteine and the mortality of patients with sepsis, and to provide new indicators for accurately judging the prognosis of sepsis , To provide new targets for clinical development of drugs for the treatment of sepsis.

Establishing an antibiotic policy based on the local culture sensitivity records to ensure rational use of antibiocs, then measure the clinical and economic impact of this local antibiotic policy.

This ancillary study determines whether the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) [ClinicalTrials.gov Identifier: NCT03434028] treatment arms (restrictive fluids strategy vs. liberal fluid strategy) for early sepsis-induced hypotension are associated with differences in cardiac structure and function based on an echocardiogram at 24 hours after randomization. Secondarily, this ancillary study explores possible heterogeneity of treatment effect based on an echocardiogram performed shortly after randomization in CLOVERS.