• Fat
• Inflammation
• Lipids
• Lipopolysaccharide
• Taste buds

• Animals
• Mice
• Endotoxemia/chemically induced
• Interleukin-6/genetics
• Lipopolysaccharides/toxicity
• Tumor Necrosis Factor-alpha
• Anti-Inflammatory Agents/pharmacology
• Anti-Inflammatory Agents/therapeutic use
• Inflammation
• CD36 Antigens/genetics
• Cytokines/genetics
• Interleukin-1beta/genetics
• RNA, Messenger
• Fatty Acids

• facilitators and barriers
• nurse
• perceived barriers
• sepsis
• sepsis six guidelines

• Traditional Chinese Medicine
• active ingredients
• chemical structure
• monomers.
• natural drugs
• sepsis

• Sepsis/drug therapy
• Humans
• Medicine, Chinese Traditional
• Biological Products/chemistry
• Biological Products/pharmacology
• Biological Products/therapeutic use
• Drugs, Chinese Herbal/chemistry
• Drugs, Chinese Herbal/pharmacology
• Drugs, Chinese Herbal/therapeutic use
• Animals

• 2022T150393,2021M690099 China Postdoctoral Science Foundation
• ZR2020QH309,82004277 National Natural Science Foundation of China (NSFC)

• Department pharmacists
• Emergency
• Sepsis Compliance
• Sepsis Tracking Sheet
• Sepsis core measures

• Humans
• Prospective Studies
• Pharmacists
• Retrospective Studies
• Sepsis
• Emergency Service, Hospital
• Shock, Septic

• DOCK8
• aerobic glycolysis
• immune function
• neutrophils
• sepsis

• Male
• Animals
• Mice
• Neutrophils
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Sepsis
• Immunity
• Glycolysis
• Adenosine Triphosphate

• Adult
• Humans
• Retrospective Studies
• Prognosis
• Sepsis
• ROC Curve
• Intraabdominal Infections
• Lactic Acid
• Acute Kidney Injury
• Peptide Fragments
• Lipopolysaccharide Receptors

• caspase-11 4
• goitrin 1
• lipopolysaccharide 3
• pyroptosis 5
• septic shock 2

• No. ZY (2021-2023)-0215 The Program of Shanghai Municipal Commission of Health and Family Planning
• No. ZYYCXTD-D-202004 Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine

There were few studies on the prognosis of tumor patients with sepsis after gastrointestinal surgery and there was no relevant nomogram for predicting the prognosis of these patients.

To establish a nomogram for predicting the prognosis of tumor patients with sepsis after gastrointestinal surgery in the intensive care unit (ICU).

A total of 303 septic patients after gastrointestinal tumor surgery admitted to the ICU at Peking University Cancer Hospital from January 1, 2013 to December 31, 2020 were analysed retrospectively. The model for predicting the prognosis of septic patients was established by the R software package.

The most common infection site of sepsis after gastrointestinal surgery in the ICU was abdominal infection. The 90-d all-cause mortality rate was 10.2% in our study group. In multiple analyses, we found that there were statistically significant differences in tumor type, septic shock, the number of lymphocytes after ICU admission, serum creatinine and total operation times among tumor patients with sepsis after gastrointestinal surgery (P < 0.05). These five variables could be used to establish a nomogram for predicting the prognosis of these septic patients. The nomogram was verified, and the initial C-index was 0.861. After 1000 internal validations of the model, the C-index was 0.876, and the discrimination was good. The correction curve indicated that the actual value was in good agreement with the predicted value.

The nomogram based on these five factors (tumor type, septic shock, number of lymphocytes, serum creatinine, and total operation times) could accurately predict the prognosis of tumor patients with sepsis after gastrointestinal surgery.

• Tumor
• Surgery
• Sepsis
• Gastrointestinal
• Nomogram

There is a large body of evidence showing that delayed initiation of sepsis bundle is associated with adverse clinical outcomes in patients with sepsis. However, it is controversial whether electronic automated alerts can help improve clinical outcomes of sepsis. Electronic databases are searched from inception to December 2021 for comparative effectiveness studies comparing automated alerts versus usual care for the management of sepsis. A total of 36 studies are eligible for analysis, including 6 randomized controlled trials and 30 non-randomized studies. There is significant heterogeneity in these studies concerning the study setting, design, and alerting methods. The Bayesian meta-analysis by using pooled effects of non-randomized studies as priors shows a beneficial effect of the alerting system (relative risk [RR]: 0.71; 95% credible interval: 0.62 to 0.81) in reducing mortality. The automated alerting system shows less beneficial effects in the intensive care unit (RR: 0.90; 95% CI: 0.73–1.11) than that in the emergency department (RR: 0.68; 95% CI: 0.51–0.90) and ward (RR: 0.71; 95% CI: 0.61–0.82). Furthermore, machine learning-based prediction methods can reduce mortality by a larger magnitude (RR: 0.56; 95% CI: 0.39–0.80) than rule-based methods (RR: 0.73; 95% CI: 0.63–0.85). The study shows a statistically significant beneficial effect of using the automated alerting system in the management of sepsis. Interestingly, machine learning monitoring systems coupled with better early interventions show promise, especially for patients outside of the intensive care unit.

Effective removal of pathogenic bacteria is key to improving the prognosis of sepsis. Polymorphonuclear neutrophils (PMNs) are the most important components of innate cellular immunity and play vital roles in clearing pathogenic bacteria. However, the metabolic characteristics and immunomodulatory pathways of PMNs during sepsis have not been investigated. In the present study, we explored the immune metabolism characteristics of PMNs and the mechanism by which neutrophilic glycolysis is regulated during sepsis.

Metabolomics analysis was performed on PMNs isolated from 14 septic patients, 26 patients with acute appendicitis, and 19 healthy volunteers. Transcriptome analysis was performed on the PMNs isolated from the healthy volunteers and the patients with sepsis to assess glycolysis and investigate its mechanism. Lipopolysaccharide (LPS) was used to stimulate the neutrophils isolated from the healthy volunteers at different time intervals to build an LPS-tolerant model. Chemotaxis, phagocytosis, lactate production, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) were evaluated.

Transcriptomics showed significant changes in glycolysis and the mTOR/HIF-1α signaling pathway during sepsis. Metabolomics revealed that the Warburg effect was significantly altered in the patients with sepsis. We discovered that glycolysis regulated PMNs’ chemotaxis and phagocytosis functions during sepsis. Lactate dehydrogenase A (LDHA) downregulation was a key factor in the inhibition of glycolysis in PMNs. This study confirmed that the PI3K/Akt-HIF-1α pathway was involved in the LDHA expression level and also influenced PMNs’ chemotaxis and phagocytosis functions.

The inhibition of glycolysis contributed to neutrophil immunosuppression during sepsis and might be controlled by PI3K/Akt-HIF-1α pathway-mediated LDHA downregulation. Our study provides a scientific theoretical basis for the management and treatment of patients with sepsis and promotes to identify therapeutic target for the improvement of immune function in sepsis.

The online version contains supplementary material available at 10.1186/s13054-022-03893-6.

Sepsis is a common cause of emergency department (ED) presentation and hospital admission, accounting for a disproportionate number of deaths each year relative to its incidence. Sepsis outcomes have improved with increased recognition and treatment standards promoted by the Surviving Sepsis Campaign. Due to delay in recognition and other barriers, sepsis bundle compliance remains low nationally. We hypothesised that a targeted education intervention regarding use of an electronic health record (EHR) tool for identification and management of sepsis would lead to increased EHR tool utilisation and increased sepsis bundle compliance.

We created a multidisciplinary quality improvement team to provide training and feedback on EHR tool utilisation within our ED. A prospective evaluation of the rate of EHR tool utilisation was monitored from June through December 2020. Simultaneously, we conducted two retrospective cohort studies comparing overall sepsis bundle compliance for patients when EHR tool was used versus not used. The first cohort was all patients with intention-to-treat for any sepsis severity. The second cohort of patients included adult patients with time of recognition of sepsis in the ED admitted with a diagnosis of severe sepsis or septic shock.

EHR tool utilisation increased from 23.3% baseline prior to intervention to 87.2% during the study. In the intention-to-treat cohort, there was a statistically significant difference in compliance between EHR tool utilisation versus no utilisation in overall bundle compliance (p<0.001) and for several individual components: initial lactate (p=0.009), repeat lactate (p=0.001), timely antibiotics (p=0.031), blood cultures before antibiotics (p=0.001), initial fluid bolus (p<0.001) and fluid reassessment (p<0.001). In the severe sepsis and septic shock cohort, EHR tool use increased from 71.2% pre-intervention to 85.0% post-intervention (p=0.008).

With training, feedback and EHR optimisation, an EHR tool can be successfully integrated into current workflows and appears to increase sepsis bundle compliance.

• computerised
• critical care
• decision support
• emergency department
• quality improvement
• standards of care

• Acute lung injury
• Autophagy
• Ferroptosis
• Hydrogen sulfide

• Adult
• Aged
• Aged, 80 and over
• Biomarkers/blood
• Calcitonin/blood
• Circulating MicroRNA/genetics
• Cohort Studies
• Early Diagnosis
• Female
• Gene Expression/genetics
• Humans
• Male
• MicroRNAs/genetics
• Middle Aged
• Procalcitonin/blood
• Prognosis
• ROC Curve
• Sepsis/diagnosis
• Sepsis/genetics
• Shock, Septic/diagnosis
• Shock, Septic/genetics
• Transcriptome/genetics
• Vietnam/epidemiology

• National Foundation for Science and Technology Development

• Community-acquired infections
• Control del foco
• Early mortality
• ICU
• Infecciones adquiridas en la comunidad
• Mortalidad precoz
• Septic shock
• Shock séptico
• Source control
• UCI

• Humans
• Intensive Care Units
• Retrospective Studies
• Risk Factors
• Sepsis
• Shock, Septic

• antibiotic management
• quality improvement
• sepsis

• National early warning score
• infection
• meta-analysis
• qSOFA
• sepsis

• Antigen
• Immunoglobulins
• Immunology
• Infectious disease

• Animals
• Antigens/genetics
• Antigens/immunology
• B-Lymphocytes/immunology
• Dendritic Cells, Follicular/immunology
• Immunity, Humoral
• Mice
• Mice, Knockout
• Sepsis/genetics
• Sepsis/immunology
• T-Lymphocytes/immunology

• P01 AI102852 NIAID NIH HHS
• R35 GM118182 NIGMS NIH HHS

• Ruscogenin
• acute lung injury
• cecal ligation and puncture
• endothelial barrier
• sepsis
• toll-like receptor 4

• data analytics
• artificial intelligence
• nursing research
• outcome and process assessment

• Artificial Intelligence
• Data Science
• Delivery of Health Care
• Humans

• K12 HS026395 AHRQ HHS

The central component of sepsis pathogenesis is inflammatory disorder, which is related to dysfunction of the immune system. However, the specific molecular mechanism of sepsis has not yet been fully elucidated. The aim of our study was to identify genes that are significantly changed during sepsis development, for the identification of potential pathogenic factors. Differentially expressed genes (DEGs) were identified in 88 control and 214 septic patient samples. Gene ontology (GO) and pathway enrichment analyses were performed using David. A protein-protein interaction (PPI) network was established using STRING and Cytoscape. Further validation was performed using real-time polymerase chain reaction (RT-PCR). We identified 37 common DEGs. GO and pathway enrichment indicated that enzymes and transcription factors accounted for a large proportion of DEGs; immune system and inflammation signaling demonstrated the most significant changes. Furthermore, eight hub genes were identified via PPI analysis. Interestingly, four of the top five upregulated and all downregulated DEGs were involved in immune and inflammation signaling. In addition, the most intensive hub gene AKT1 and the top DEGs in human clinical samples were validated using RT-PCR. This study explored the possible molecular mechanisms underpinning the inflammatory, immune, and PI3K/AKT pathways related to sepsis development.

There have been different reports on mortality of sepsis; however, few focus on the prognosis of patients with sepsis after surgery.

To study the clinical features and prognostic predictors in patients with sepsis after gastrointestinal tumor surgery in intensive care unit (ICU).

We retrospectively screened patients who underwent gastrointestinal tumor surgery at Peking University Cancer Hospital from January 2015 to December 2019. Among them, 181 patients who were diagnosed with sepsis in ICU were included in our study. Survival was analysed by the Kaplan-Meier method. Univariate and multivariate adjusted analyses were performed to identify predictors of prognosis.

The 90-d all-cause mortality rate was 11.1% in our study. Univariate analysis showed that body mass index (BMI), shock within 48 h after ICU admission, leukocyte count, lymphocyte to neutrophil ratio, international normalized ratio, creatinine, procalcitonin, lactic acid, oxygenation index, and sequential organ failure assessment (SOFA) score within 24 h after ICU admission might be all significantly associated with the prognosis of sepsis after gastrointestinal tumor surgery. In multiple analysis, we found that BMI ≤ 20 kg/m², lactic acid after ICU admission, and SOFA score within 24 h after ICU admission might be independent risk predictors of the prognosis of sepsis after gastrointestinal tumor surgery. Compared with SOFA score, SOFA score combined with BMI and lactic acid might have higher predictive ability (area under the receiver operating characteristic curve, 0.859; 95% confidence interval, 0.789-0.929).

Lactic acid and SOFA score within 24 h after ICU admission are independent risk predictors of the prognosis of sepsis after gastrointestinal tumor surgery. SOFA score combined with BMI and lactic acid might have good predictive value.

• Surgery
• Sepsis
• Gastrointestinal
• Prognosis
• Post-operative

Compliance with the surviving sepsis campaign (SSC) guidelines (C_ssc) is a key factor affecting the effects of sepsis treatment. We designed this study to investigate the relationships of the structure indicators of ICU on 3 and 6-h C_ssc in China.

A total of 1854 hospitals were enrolled in a survey, led by the China National Critical Care Quality Control Center (China-NCCQC) from January 1, 2018, through December 31, 2018. We investigated the 1854 hospitals’ 3 and 6-h C_ssc, including compliance with each specific measure of the 3-h and 6-h SSC bundles. We also investigated the actual level of the structure indicators of ICU, released by China-NCCQC in 2015.The outcomes were in adherence with the SSC guidelines (2016). Monitoring indicators included 3 and 6-h C_ssc.

In the subgroup, the rate of broad-spectrum antibiotic therapy was the highest, and the rate of CVP and ScvO2 measurement was the lowest among the items of 3 and 6-h C_ssc. Structure indicators related to 3 and 6-h C_ssc include the predicted mortality rate and the standardized mortality ratio (SMR). The relationships between 3 and 6-h C_ssc and the proportion of ICU in total inpatient bed occupancy, the proportion of acute physiology and chronic health evaluation (APACHE) II score ≥ 15 in all ICU patients were uncertain. There was no relationship of 3 and 6-h C_ssc with the proportion of ICU patients among total inpatients.

Structure indicators influencing 3 and 6-h C_ssc in China are the predicted mortality rate and the standardized mortality rate.

The online version contains supplementary material available at 10.1186/s40001-021-00498-7.

• China
• Compliance
• ICU
• Structure indicator
• Surviving sepsis campaign guidelines

• antibiotics
• quality improvement
• sepsis
• time-to-antibiotics

• Acute lung injury
• Hydrogen sulfide
• NLRP3
• PDGFRβ
• Sepsis

• alkaline phosphatase
• bilirubin
• cholestasis
• hypoxic hepatitis
• transaminase

• Community-acquired infections
• Control del foco
• Early mortality
• ICU
• Infecciones adquiridas en la comunidad
• Mortalidad precoz
• Septic shock
• Shock séptico
• Source control
• UCI

To investigate the global burden of sepsis in hospitalized adults by updating and expanding a systematic review and meta-analysis and to compare findings with recent Institute for Health Metrics and Evaluation (IHME) sepsis estimates.

Thirteen electronic databases were searched for studies on population-level sepsis incidence defined according to clinical criteria (Sepsis-1, -2: severe sepsis criteria, or sepsis-3: sepsis criteria) or relevant ICD-codes. The search of the original systematic review was updated for studies published 05/2015–02/2019 and complemented by a search targeting low- or middle-income-country (LMIC) studies published 01/1979–02/2019. We performed a random-effects meta-analysis with incidence of hospital- and ICU-treated sepsis and proportion of deaths among these sepsis cases as outcomes.

Of 4746 results, 28 met the inclusion criteria. 21 studies contributed data for the meta-analysis and were pooled with 30 studies from the original meta-analysis. Pooled incidence was 189 [95% CI 133, 267] hospital-treated sepsis cases per 100,000 person-years. An estimated 26.7% [22.9, 30.7] of sepsis patients died. Estimated incidence of ICU-treated sepsis was 58 [42, 81] per 100,000 person-years, of which 41.9% [95% CI 36.2, 47.7] died prior to hospital discharge. There was a considerably higher incidence of hospital-treated sepsis observed after 2008 (+ 46% compared to the overall time frame).

Compared to results from the IHME study, we found an approximately 50% lower incidence of hospital-treated sepsis. The majority of studies included were based on administrative data, thus limiting our ability to assess temporal trends and regional differences. The incidence of sepsis remains unknown for the vast majority of LMICs, highlighting the urgent need for improved epidemiological sepsis surveillance.

The online version of this article (10.1007/s00134-020-06151-x) contains supplementary material, which is available to authorized users.

• Burden
• Epidemiology
• Incidence
• Mortality
• Sepsis

• Imipenem
• Infectious disease
• Infusion mode
• Minimal inhibitory concentration
• Pharmacokinetic/pharmacodynamic
• Sepsis

• Administration, Intravenous
• Aged
• Anti-Bacterial Agents/administration & dosage
• Anti-Bacterial Agents/pharmacokinetics
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Humans
• Imipenem/administration & dosage
• Imipenem/pharmacokinetics
• Male
• Microbial Sensitivity Tests/methods
• Middle Aged
• Sepsis/drug therapy
• Shock, Septic/drug therapy
• Treatment Outcome

• Merck & Co., Inc.

• pregnancy
• postpartum
• risk factors
• sepsis
• infection
• readmission

• Adult
• Burns/therapy
• Child
• Humans

Sepsis is an acute, often fatal syndrome that requires early diagnosis and proper treatment. Blood culture (BC) is the gold standard for the identification of pathogens, however it has marked limitations, including that it is time-consuming (delaying treatment) and can only detect microbes that readily grow under culture conditions. Alternatively, non-culture-based methodologies like polymerase chain reaction (PCR) are faster but also have limitations; e.g., the reaction is often inhibited by the abundance of human DNA and thus can only detect limited known target pathogens. In our previous publication, we have demonstrated a proof-of-concept of a simple pre-analytical tool to remove human DNA from patients’ blood specimens, hence allowing downstream PCRs to detect rare bacterial genetic materials. In the current study, we reported a better performance of a novel prototype diagnosis kit named Sepsis@Quick that combines human DNA removal step with real-time PCRs compared to blood-culture for identifying sepsis causative bacteria. Our data showed that Sepsis@Quick is superior to blood culture in which the novel diagnostic kit could identify more pathogens and even polymicrobial infection, faster and less influenced by the empirical administration of broad spectrum antibiotic therapy (single administration or combination of cephalosporin III and fluoroquinolon). Additionally, for the first time, we demonstrated that positive results achieved by Sepsis@Quick are significantly associated with a reduction of sepsis-related mortality.

Raising public awareness of sepsis, a potentially life-threatening dysregulated host response to infection, to hasten its recognition has become a major focus of physicians, investigators, and both non-governmental and governmental agencies. While the internet is a common means by which to seek out healthcare information, little is understood about patterns and drivers of these behaviors. We sought to examine traffic to Wikipedia, a popular and publicly available online encyclopedia, to better understand how, when, and why users access information about sepsis. Utilizing pageview traffic data for all available language localizations of the sepsis and septic shock pages between July 1, 2015 and June 30, 2018, significantly outlying daily pageview totals were identified using a seasonal hybrid extreme studentized deviate approach. Consecutive outlying days were aggregated, and a qualitative analysis was undertaken of print and online news media coverage to identify potential correlates. Traffic patterns were further characterized using paired referrer to resource (i.e. clickstream) data, which were available for a temporal subset of the pageviews. Of the 20,557,055 pageviews across 65 linguistic localizations, 47 of the 1,096 total daily pageview counts were identified as upward outliers. After aggregating sequential outlying days, 25 epochs were examined. Qualitative analysis identified at least one major news media correlate for each, which were typically related to high-profile deaths from sepsis and, less commonly, awareness promotion efforts. Clickstream analysis suggests that most sepsis and septic shock Wikipedia pageviews originate from external referrals, namely search engines. Owing to its granular and publicly available traffic data, Wikipedia holds promise as a means by which to better understand global drivers of online sepsis information seeking. Further characterization of user engagement with this information may help to elucidate means by which to optimize the visibility, content, and delivery of awareness promotion efforts.

• Humans
• Information Seeking Behavior
• Internet
• Language
• Retrospective Studies
• Sepsis/epidemiology
• Shock, Septic/epidemiology

Sepsis is characterized by a systemic inflammatory response followed by immunosuppression of the host. Metabolic defects and mitochondrial failure are common in immunocompromised patients with sepsis. The NLRP3 inflammasome is important for establishing an inflammatory response after activation by the purinergic P2X7 receptor. Here, we study a cohort of individuals with intra-abdominal origin sepsis and show that patient monocytes have impaired NLRP3 activation by the P2X7 receptor. Furthermore, most sepsis-related deaths are among patients whose NLRP3 activation is profoundly altered. In monocytes from sepsis patients, the P2X7 receptor is associated with mitochondrial dysfunction. Furthermore, activation of the P2X7 receptor results in mitochondrial damage, which in turn inhibits NLRP3 activation by HIF-1α. We show that mortality increases in a mouse model of sepsis when the P2X7 receptor is activated in vivo. These data reveal a molecular mechanism initiated by the P2X7 receptor that contributes to NLRP3 impairment during infection.

Systemic sepsis is a potentially life-threatening illness and immunocompromised individuals are especially vulnerable. Here, using a cohort of patients with intra-abdominal origin sepsis, the authors show an important role for the NLRP3 inflammasome in establishing a host response, and NLRP3 dysfunction is a common feature of sepsis mortality.

• organ failure
• sepsis
• septic shock

• Intracranial hemorrhage
• Stroke
• Transient ischemic attack
• Trends

• angiotensin ii
• critical care
• drug development and approval
• hemodynamics
• sepsis
• vasoconstrictors

Sepsis is recognized as a life-threatening organ dysfunctional disease that is caused by dysregulated host responses to infection. Up to now, sepsis still remains a dominant cause of multiple organ dysfunction syndrome (MODS) and death among severe condition patients. Pyroptosis, originally named after the Greek words “pyro” and “ptosis” in 2001, has been defined as a specific programmed cell death characterized by release of inflammatory cytokines. During sepsis, pyroptosis is required for defense against bacterial infection because appropriate pyroptosis can minimize tissue damage. Even so, pyroptosis when overactivated can result in septic shock, MODS, or increased risk of secondary infection. Proteolytic cleavage of gasdermin D (GSDMD) by caspase-1, caspase-4, caspase-5, and caspase-11 is an essential step for the execution of pyroptosis in activated innate immune cells and endothelial cells stimulated by cytosolic lipopolysaccharide (LPS). Cleaved GSDMD also triggers NACHT, LRR, and PYD domain-containing protein (NLRP) 3-mediated activation of caspase-1 via an intrinsic pathway, while the precise mechanism underlying GSDMD-induced NLRP 3 activation remains unclear. Hence, this study provides an overview of the recent advances in the molecular mechanisms underlying pyroptosis in sepsis.