Sepsis

The goal of this pilot clinical trial is to learn if a fluid assessment using non-invasive cardiac output monitoring (NICOM) is helpful for patients with sepsis who have low blood pressure in the Emergency Department (ED). The study will measure whether the NICOM assessment changes fluid resuscitation practices and is feasible in the ED setting. All patients will receive standard medical care. Patients assigned to the NICOM group will receive a one-time, non-invasive bedside fluid assessment using NICOM, in addition to standard care, and the results of the fluid assessment will be provided to the treating physician.

Researchers are looking for a better way to treat people who have sepsis induced coagulopathy. Sepsis happens when bacteria and their toxins spread in the blood, causing an infection. To overcome the infection the body responds activating the immune system, sometimes this immune response is too active and causes uncontrolled blood clot formation, also called sepsis-induced coagulopathy. Sepsis coagulopathy damages blood vessels and organs and leads to low platelet levels in the body. In severe cases, it can even lead to death. The main purpose of this first in patient study is to learn about how safe BAY 3389934 is, its suitable dose, and how it affects the participants with sepsis induced coagulopathy. For this study, researchers will enroll people receiving treatment for sepsis induced coagulopathy in a hospital intensive care unit (ICU). For this, the researchers will collect the number of participants with medical problems during and after receiving BAY 3389934. These medical problems are also known as "adverse events". Doctors keep track of all medical problems that happen in studies, even if they do not think they might be related to the study treatments. Participants will be divided into 2 groups. The first group will receive the lowest starting dose of BAY3389934. The researcher will carefully monitor how the participant responds to the medication and may adjust the dose, either increasing or decreasing it based on the safety and the tolerability of the drug. If no serious side effects are reported from the first group, the second group will receive higher dose of BAY3389934. Each participant will be in the study for around 28 days. During the study, the doctors and their study team will: * Take blood and urine samples, * Do physical examinations, * Check vital signs such as body temperature, blood pressure and heart rate, * Examine heart health using electrocardiogram (ECG)

This study will investigate whether a family-centered intervention that has been adapted for patients with critical illness and their caregivers is possible, acceptable, and helpful

Adverse outcomes in surgical sepsis patients are secondary to dysregulated emergency myelopoiesis, and expansion of myeloid-derived suppressor cells. Here we propose to determine the underlying mechanisms behind the increased expansion of these leukocyte populations and the underlying mechanisms that drive inflammation and immune suppression.

The VPT Safety Trial (VPS) compares two common antibiotic combinations to see how they affect the kidneys of patients in the hospital with serious infections. Both combinations are approved by the Food and Drug Administration (FDA). The goal is to help doctors know which combination is safer so they can make better choices for their patients.

In septic shock, restoring large-vessel (macrocirculatory) perfusion-reflected by a normal capillary refill time (CRT)-does not always mean that oxygen use at the tissue level has recovered. This mismatch, sometimes called loss of hemodynamic coherence, may be detectable by comparing CRT with the oxygen extraction ratio (O₂ER), a marker of how much oxygen the tissues are extracting from the blood. Patients whose CRT has normalized but whose O₂ER remains abnormal-either too high (suggesting oxygen delivery that is insufficient for demand) or too low (suggesting microcirculatory shunting)-are considered to have a "discordant" perfusion phenotype. This prospective, single-center, observational cohort study aims to determine how often this CRT-O₂ER discordance occurs at the 6th hour of resuscitation in adult patients with septic shock, and whether it is associated with 28-day mortality. Approximately 100 consecutive adult patients diagnosed with septic shock (with pre-existing central venous and arterial catheters) will be followed. Clinical and laboratory measurements-including CRT, O₂ER, lactate, mottling score, and organ dysfunction scores-will be recorded at hours 0, 6, 12, and 24, with the main phenotype grouping performed at hour 6. The study is purely observational: CRT is a painless, non-invasive bedside measurement, and O₂ER is calculated from blood gas samples already drawn as part of routine care, so no additional interventions or blood draws are performed for research purposes.

This study aims to assess the efficacy of a new biomarker, N6-threonylcarbamoyladenosine (t6A), for the early diagnosis of Early-Onset Sepsis (EOS) in newborns.

Study Hypothesis/Question In infants born very preterm, advancing enteral feeds after 24 hours from birth (limited trophic feeds) versus after 72 hours (extended trophic feeds) reduces the risk of all-cause late onset sepsis (LOS) without increasing the risk of other adverse outcomes. Study Design Type This is a multi-center, open-label, parallel-group, individual randomized controlled trial comparing two different trophic feeding regimens in preterm infants born between 25w0d and 31w6d. These infants will be randomly assigned to either the intervention group, receiving limited trophic feeding (20 to 25 mL/kg/day for one day) or the control group, receiving extended trophic feeding (20 to 25 mL/kg/day for three days) prior to advancing enteral feeds until full feeding volume (140 mL/kg/day) is achieved. Eligibility Criteria Preterm infants with gestational ages between 25 0/7 and 31 6/7 weeks and a birthweight of \<1500 grams who are admitted to six participating neonatal units will be eligible for inclusion. Infants with \<5th percentile for weight at birth, vasopressor use within first 24 hours of life major congenital/genetic anomalies affecting enteral feeding, growth, or mortality, and those with a terminal illness in which decisions to withhold or limit support have been made will be excluded. Infants of parents or legal guardians who are unable to provide consent within 36 hours of birth will also be excluded. Study Intervention/Methods Written parental informed consent will be obtained prenatally or within the first 36 hours of birth. Infants will be randomized to receive limited trophic feeds of 24 to 36 hours or extended trophic feeds for 72 hours prior to the advancement of enteral feeds. Infants will be fed parent's own milk (POM) with donor human milk as the alternative if POM is unavailable. Primary Outcome Late-onset sepsis, defined as positive blood, urine, and/or cerebrospinal fluid (CSF) cultures in the presence of compatible clinical signs of sepsis, occurring after postnatal day 3 and before hospital discharge, and treated with antibiotics for 5 days or more. Secondary Outcome(s) The trial will assess various secondary outcomes including length of hospital stay, all-cause in-hospital mortality, duration of IV fluids and central line utilization, necrotizing enterocolitis (Bell's stage IIa or higher), severe intraventricular hemorrhage (grade III or IV either unilaterally or bilaterally), bronchopulmonary dysplasia (oxygen requirement or positive pressure ventilation at 36 weeks corrected gestational age), or retinopathy of prematurity requiring intervention. Additionally, growth metrics throughout hospitalization will be evaluated using change in weight, length, and head circumference z-scores from birth to 36 weeks' corrected gestational age between infants in the limited and extended trophic feeding groups. We will also evaluate the 2 year developmental outcomes of a subset of participants who consent to follow up. This will include the Bayley Scales of Infant and Toddler Development-4th edition Language, Cognitive, and Motor domain scores at 2 years corrected age.

This pilot study will evaluate whether a rapid point-of-care blood test can help identify early signs of infection and sepsis in preterm infants. The study will include preterm infants born before 37 weeks of pregnancy who are admitted to the neonatal care unit and have a suspected infection. The researchers will measure several substances in the blood that can increase during infection, including interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP), and myxovirus resistance protein A (MxA). Results obtained with the point-of-care device will be compared with standard laboratory measurements. The researchers will also study whether measuring IL-6 and PCT during the first 12 hours of life may provide useful information about infection earlier than CRP testing and whether combined MxA and CRP measurements may help distinguish bacterial from viral infections. This is an observational study and will not change the infants' standard medical care or treatment. Results from the point-of-care device will not be used to make treatment decisions during the study. Blood samples will be collected as part of, or together with, routine blood sampling whenever possible. The study is expected to include approximately 40 preterm infants, with a maximum of 80 infants enrolled.

Sepsis occurs when an infection, caused by bacteria, a virus, or a fungus, enters the body and throws the immune system out of balance. Instead of protecting the body, the immune response may become too strong and start damaging healthy organs, or it may become too weak and fail to control the infection. Both situations can be life-threatening. Even people who survive sepsis may experience long-term health problems, such as new infections, heart and blood vessel diseases, or early death. This study aims to better understand how the immune system behaves during and after sepsis. We believe that there are different types of immune responses in sepsis, called immunotypes. We will identify these immunotypes by examining substances in the blood and changes in immune cells. We will then study which immunotypes help protect patients and which may cause short- or long-term harm. Understanding these immunotypes may make it possible in the future to quickly determine what type of immune response a patient with sepsis has. This could help doctors choose the best treatment for each individual patient. A total of 400 patients with sepsis from the intensive care unit will take part in this study. We will collect blood samples at several time points and gather information about their health. Participants will be followed from their intensive care admission until one year after they return home.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-attributable mortality in sub-Saharan Africa (sSA) is high, with in-hospital mortality in some settings approaching 40%. Studies show that mortality among children under 5 years hospitalized with sepsis remains high within the first 6 months of discharge. Additionally, high mortality has been observed among other populations within sSA, with factors such as HIV infection being associated with increased risk. Reducing sepsis deaths contributes to the achievement of the Sustainable Development Goals (SDG), particularly SDG 3 in reducing maternal mortality (3.1), neonatal and under five mortality (3.2), and burden of mortality from communicable diseases (3.3) and improving universal health coverage (3.8). The World Health Organization (WHO) has recognized sepsis as a global priority, with low- and middle-income settings being particularly affected. In sSA, sepsis is commonly associated with infectious diseases like malaria, Human Immunodeficiency Virus/ Acquired Immunodeficiency Syndrome (HIV/AIDS), pneumonia, tuberculosis, and diarrhea. Guidelines from the Surviving Sepsis Campaign (SSC) have become standard in some settings. However, little is known about patients' status post-discharge. This study aims to evaluate two post-discharge follow-up strategies for adult sepsis patients. Study duration is 45 months, participants will receive intervention up to 90 days post discharge. Description of intervention: Post-discharge follow-up strategy 1: Enhanced Discharge Intervention (EDI) Post-discharge follow-up strategy 2: EDI plus Interactive Voice Response (IVR) \*All participants will receive a feature phone. Objectives: The study aims to evaluate two post-discharge follow-up strategies for adult patients hospitalized with sepsis, focusing on their efficacy in reducing the 90-day mortality, and their effect on return to follow-up, number of re-admissions, and quality of life. Primary efficacy endpoint * 90- day all-cause mortality post discharge Secondary end points * Time to death * 28-day all-cause mortality * Attendance within 14-day check-up post discharge * Re-admission within 28 and 90 days * Days alive and out of hospital (DAOH) * Quality of life score (Baseline vs 28 day and Baseline vs 90 days) * Differences in baseline demographic and clinical characteristics (e.g., age, sex, disease severity, comorbidities, key laboratory values) between randomized participants and screen failures. Study design: This is an open-label, randomized, parallel, interventional study, with two post-discharge follow-up strategies: 1) EDI; or 2) EDI plus IVR system. Fixed allocation randomization at a 1:1 ratio will be applied to either study arm. Sample size: A total of 1,410 (705 per arm) from the four countries (Uganda, Nigeria, Ghana and Mozambique) will be enrolled competitively across the sites.

This is a study comparing 3 years of retrospective data (pre-implementation) to 2 years of prospective data after the implementation of a pediatric version of Electronic Cardiac Arrest Risk Triage (pediatric eCART), a clinical decision support (CDS) tool that uses electronic health records (EHR) to identify patients with high risk for life threatening outcomes. Up to 30,000 encounters with pediatric patients will be assessed. Acceptability of the pediatric eCART intervention will also be measured from pediatric nurse clinicians.

To characterize the electroencephalogram (EEG) features of sepsis patients with distinct inflammatory response phenotypes, dynamically track their evolutionary trajectories, and analyze their associations with long-term changes in cognitive function.

This study aims to evaluate the effects of an individualized enteral nutrition formula on clinical outcomes in critically ill adult patients in the intensive care unit (ICU). Participants will be randomly assigned to one of two groups: the individualized nutrition group or the standard nutrition group. In the individualized group, the total daily amount of enteral nutrition will be calculated and adjusted daily based on the patient's resting energy expenditure (measured by indirect calorimetry) and serum protein levels. In the standard group, a fixed-dose formula will be administered according to routine clinical protocols recommended by current guidelines. The intervention will be initiated within 48 hours of ICU admission and continued for up to 14 days or until ICU discharge. The study will assess clinical prognosis, as well as changes in gut and pulmonary microbiota, serum metabolomics, and macronutrient balance. The findings may provide evidence for personalized nutrition strategies in critically ill patients.

This study seeks to develop early recognition tools specially designed for children meeting the Phoenix definition and explore implementation science aspects by investigating facilitators and barriers to adopting Phoenix sepsis criteria in clinical practice. This addresses the critical need for systemic, evidence-based approaches to paediatric sepsis identification across diverse healthcare settings in Asia.

To evaluate the value of biomarkers of neuronal and glial injury for predicting cognitive impairment (memory impairment assessed by a MoCA score \< 26/30) at 3 months in patient admitted in the intensive care unit for a sepsis or a septic shock.

This multicenter prospective observational cohort study evaluates how well the initial triage category assigned by the Turkish Ministry of Health three-level color-coded triage system (Red-Yellow-Green) predicts serious clinical outcomes in children aged 0-18 years who present with fever to pediatric emergency departments. The study additionally assesses whether physiological parameters recorded at triage (heart rate, respiratory rate, oxygen saturation, capillary refill time, AVPU level of consciousness, and general appearance) provide independent and incremental prognostic value beyond the assigned triage category. Ten centers across Turkey will enroll consecutive eligible febrile children over a 3-month period. Routine clinical care and triage decisions are not altered by the study. The primary outcome is a composite serious clinical outcome. The study is reported in accordance with the STROBE and TRIPOD statements.

The research project is an anonymous, prospective, non-interventional consensus study in the form of a modified Delphi method, consisting of three online surveys and structured feedback meetings without recording. The goal is the structured evaluation and consolidation of expert assessments to develop context-adapted quality indicators and operationalize them for early sepsis care in Sub-Saharan Africa.

Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Severe sepsis is the most common cause of death among critically ill patients in non-coronary intensive care units (ICU). Sustained excessive inflammation and immune dysfunction have been confirmed to play a key role in organ damage and early death of sepsis patients. Therefore, it is important to reduce excessive inflammatory response mediated by immune cells and pro-inflammatory cytokines in the acute phase of sepsis. Single-cell RNA sequencing performed on both septic patients and mice suggest that changes in Tcm (CD3+ CD8+ CD44+ CD127+ CD62L+) and Tem (CD3+ CD8+ CD44+ CD127+ CD62L -) in the acute phase of sepsis may play an important role in sepsis. In addition, animal researches showed that Tcm and Tem decreased decreased continuously at 24, 48 and 72h after cecal ligation and perforation (CLP) in mice, and the adoptive transfer of Tcm , sorting from spleen of mice 24h after CLP , but not Tem improved 7-day survival rate of sepsis mice. This observational study is aimed to investigate the quantity and proliferation of Tcm and Tem in the acute phase of sepsis and their correlation with severity level and mortality of septic patients in ICU.

Background: Sepsis is an illness that occurs when the body s immune system runs out of control. This can damage organs. Sepsis causes an estimated 1 in 5 deaths worldwide. In this natural history study, researchers want to learn more about how the immune system changes during sepsis. They hope this knowledge will help them find better ways to treat sepsis. Objective: To understand how sepsis affects the body over time. Eligibility People aged 18 years and older admitted to INOVA Fairfax Hospital in Virginia and who have sepsis. Design: Researchers will collect data from participants medical records. Participants will have blood drawn at least 5 times while they are in the hospital. Blood may be collected for up to 30 days, if they remain in the hospital that long. The blood will be taken from access lines that are already in place. Some blood draws will be optional. Participants may opt to have up to 3 tests of their heart function while they are in the hospital. Some participants may have a sample of fluid collected from their lungs. Participants will have a follow-up visit about 90 days after they join the study. This visit will be by phone call if they have left the hospital. They will fill out a questionnaire. They will answer questions about their health and how they feel. The call will last about 30 minutes....

This study will enroll adults aged 18 to 80 years diagnosed with sepsis due to a suspected or confirmed bacterial infection, within 7 days of being admitted to the hospital, and who have also developed acute kidney injury within 72 hours of the onset of sepsis. Eligible participants will be randomly assigned to receive either AZD4144 or a placebo intravenously once daily for the number of days specified in the CSP. During this Treatment Period, participants will undergo daily safety monitoring, as well as blood and urine sample collection and other assessments. After the Treatment Period, participants will continue to be monitored for safety and other assessments during each additional day they remain hospitalized (if applicable) as well as during up to 2 follow up visits after discharge. The main goal is to compare specific kidney function measurements between those participants receiving AZD4144 and those receiving the placebo.

Sepsis is a life-threatening condition caused by the body's overwhelming response to infection, and it remains a leading cause of death in intensive care units. Even when standard treatment targets such as blood pressure are met, blood flow to the small vessels of the skin and other tissues may remain impaired. This "hidden" poor perfusion may not be detected by routine monitoring, yet it may be linked to worse outcomes. The perfusion index is a simple number obtained from the standard pulse oximeter already placed on a patient's finger. It reflects blood flow in the peripheral tissues, requires no additional procedure, and causes no discomfort. This prospective observational cohort study will examine whether the perfusion index, and especially how it changes over the first 24 hours in the intensive care unit, can help predict death within 28 days in adults with sepsis or septic shock. Capillary refill time and skin mottling score will be recorded as additional bedside measures of peripheral perfusion. No treatment will be changed for the purpose of this study, and no additional blood samples or invasive procedures will be performed. All care decisions remain with the treating team. Measurements will be taken at intensive care admission and at 6 and 24 hours. Participants will be followed for 28 days, with survival status also recorded at 90 days. The study will be conducted at two centers. A prediction model will be developed in the first center and then tested, without modification, in patients enrolled at the second center.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. Septic shock represents the most severe form of sepsis and remains a leading cause of admission to intensive care units (ICUs) worldwide. It is characterized by profound circulatory, cellular, and metabolic abnormalities resulting from a dysregulated host response to infection . Despite significant advances in antimicrobial therapy, haemodynamic monitoring, organ support, and critical care management, septic shock continues to be associated with high morbidity and mortality. Patients frequently develop multiple organ dysfunction requiring prolonged ICU stay, mechanical ventilation, vasopressors support, and renal replacement therapy . Identification of modifiable risk factors that influence clinical outcomes remains a major priority in the management of septic shock. Electrolyte disturbances are common among critically ill patients, with hypophosphatemia being one of the most frequently encountered abnormalities . Serum phosphate plays a vital role in numerous physiological processes, including cellular energy production, adenosine triphosphate (ATP) synthesis, oxygen delivery through regulation of 2,3-diphosphoglycerate, membrane integrity, intracellular signaling, acid-base balance, and neuromuscular function . In septic shock, hypophosphatemia may develop because of intracellular phosphate redistribution induced by catecholamine release, respiratory alkalosis, insulin administration, aggressive fluid resuscitation, renal phosphate wasting, malnutrition, and continuous renal replacement therapy. Consequently, phosphate depletion may occur early during the course of critical illness and may persist despite standard supportive treatment . Hypophosphatemia has important clinical implications in critically ill patients. Severe phosphate deficiency impairs diaphragmatic contractility, respiratory muscle strength, myocardial performance, leukocyte function, and skeletal muscle metabolism. These abnormalities may delay liberation from mechanical ventilation, impair oxygen delivery, increase susceptibility to infection, prolong ICU stay, and adversely affect patient outcomes . Several studies have suggested that hypophosphatemia is associated with increased disease severity, prolonged mechanical ventilation, and higher mortality in critically ill patients, although the available evidence remains inconsistent, particularly among patients with septic shock. Mechanical ventilation is frequently required in septic shock because of respiratory failure, acute respiratory distress syndrome, impaired consciousness, or hemodynamic instability. Successful weaning from mechanical ventilation depends largely on adequate respiratory muscle function and sufficient cellular energy production, both of which require normal phosphate homeostasis . Hypophosphatemia may reduce diaphragmatic strength and impair respiratory muscle endurance, resulting in prolonged ventilator dependence and delayed weaning. Therefore, early recognition and correction of phosphate deficiency may represent a potentially modifiable factor capable of improving respiratory outcomes in critically ill patients . Although phosphate disturbances are well recognized in the ICU, data regarding the incidence of hypophosphatemia upon ICU admission and its relationship with the duration of mechanical ventilation in patients with septic shock remain limited, particularly in developing countries. Understanding this relationship may facilitate early identification of high-risk patients, optimize electrolyte management, improve ventilator weaning strategies, and ultimately reduce ICU morbidity and healthcare costs .

This study aims to validate a simple and reproducible index of capillary leak (CLI) in septic shock, based on haemoglobin (Hb) variation induced by standardised fluid resuscitation. To achieve this, the correlation between CLI and biomarkers of endothelial dysfunction-angiopoietin-2 and syndecan-1-will be assessed in both septic and non-septic shock patients. CLI may contribute to the individualisation of fluid management in patients with septic shock.

Sepsis is a major cause of morbidity and mortality in intensive care units. Sepsis-associated liver injury (SALI) and sepsis-associated acute kidney injury (S-AKI) are common complications associated with adverse clinical outcomes. Altered gut microbial diversity, microbial metabolites, intestinal barrier dysfunction, and systemic inflammation may contribute to hepato-renal injury during sepsis; however, prospective longitudinal evidence in patients with SALI and S-AKI remains limited. This prospective, multicenter, longitudinal observational cohort study will enroll adult patients with sepsis across five medical centers and healthy adult volunteers as a baseline reference cohort. For patients with sepsis, stool and blood samples will be collected on Day 0, Days 3-5, Days 7-10, and Days 14-20 after sepsis diagnosis. Healthy volunteers will provide a single baseline stool and blood sample at enrollment. Fecal microbial alpha diversity and community structure will be assessed by metagenomic sequencing and bioinformatic analysis. Plasma metabolites, including total short-chain fatty acids, indoxyl sulfate, and additional targeted plasma metabolites, will be measured by ultra-high-performance liquid chromatography-tandem mass spectrometry. Intestinal barrier and clinical biomarkers will also be assessed. The primary objectives are to evaluate the associations between baseline fecal microbial alpha diversity, measured by the Shannon diversity index, and SALI and S-AKI occurring within 7 days after sepsis diagnosis. Secondary objectives include evaluating the associations of baseline fecal microbial beta diversity with SALI and with S-AKI occurring within 7 days after sepsis diagnosis, characterizing longitudinal changes in fecal microbial alpha diversity, measuring plasma metabolite and intestinal biomarker concentrations at prespecified time points, and assessing 28-day all-cause mortality. Exploratory multi-omics analyses will evaluate Proteobacteria and additional microbial taxa, microbial functional genes, metabolites, and host biomarkers. This study aims to identify candidate biomarkers and biological pathways relevant to hepato-renal injury in sepsis.