Sepsis-related Mortality Research Articles

Adult Code Sepsis: A Narrative Review of its Implementation and Impact.

This narrative review explores the implementation and impact of sepsis code protocols, an urgent intervention strategy designed to improve clinical outcomes in patients with sepsis. We examined the degree of implementation, activation criteria, areas of implementation, personnel involved, responses after activation, goals and targets, impact on clinical indicators, and challenges in implementation. The reviewed evidence suggests that sepsis codes can significantly reduce sepsis-related mortality and enhance early administration of treatments. However, variability in activation criteria and inconsistent application present ongoing challenges. The review considers the incorporation of newer scoring systems, such as NEWS and MEWS, and the potential integration of machine learning tools for early sepsis detection. It highlights the importance of tailoring implementation to specific healthcare contexts and the value of ongoing training to optimize sepsis response. Limitations include the ongoing controversy surrounding sepsis definitions and the need for standardized, feasible quality indicators. Future research should focus on standardizing activation criteria, improving protocol adherence, and exploring emerging technologies to enhance early sepsis detection and management. Despite challenges, sepsis codes show promise in improving patient outcomes when implemented thoughtfully and consistently across healthcare settings.

COVID-19 and sepsis-related excess mortality in the US during the first three years: A national-wide time series study.

The COVID-19 pandemic's global impact has been devastating, causing millions of deaths. Our study investigates excess sepsis-related mortality trends over three years during the pandemic. Using CDC's National Vital Statistics System data from January 2018 to March 2023, we projected sepsis-related deaths during the pandemic using a Poisson log-linear regression model. We compared observed versus predicted deaths and analyzed temporal trends by demographics and regions. Among the 753,160 deaths documented between March 2020 and March 2023, a significant downward trend was noted in sepsis-related mortality rates from March 2022 to March 2023, coinciding with the surge of the Omicron variant. The excess mortality rates were 170.6 per million persons (95% CI: 168.2-172.6), 167.5 per million persons (95% CI: 163.6-170.9), and 73.3 per million persons (95% CI: 69.4-76.6) in the first, second, and third years, respectively. Increased sepsis-related mortality was observed across all age subgroups, with the greatest increase noted in those aged 85 years and above compared to middle- and young-aged decedents. Disparities were also observed across racial/ethnic, sex/gender subgroups, and geographic regions. This study highlights the effectiveness of current policies and prevention measures in response to the long-term circulating of SARS-CoV-2 in the community.

Racial and Ethnic Disparities in Neonatal Sepsis.

Sepsis is a significant health burden in the neonatal population. Although disparities in neonatal care have been reported, there are no data on racial/ethnic disparities in the context of sepsis. Therefore, we aimed to assess racial/ethnic disparities in the prevalence and outcomes of neonatal sepsis. The national inpatient Kids' Inpatient Database produced by the Healthcare Cost and Utilization Project was used for the year 2019. The International Classification of Diseases, 10th revision codes were used to identify the primary outcome of the neonates diagnosed with sepsis. The χ2 and Fisher tests were used to calculate odds ratios for categorical variables, and logistic regression was performed to calculate adjusted odds ratio (aOR) to account for confounders in neonatal sepsis. Of the total 3,512,817 patients, 202,103 patients with neonatal sepsis were identified across all racial and ethnic groups. Overall prevalence was statistically significant in Black [aOR, 1.13 (95% confidence interval [CI], 1.10-1.17)], Hispanic [aOR, 1.19 (95% CI, 1.15-1.22)], Asian/Pacific Islander [aOR, 1.10 (95% CI, 1.05-1.16)] and Native Americans [aOR, 1.17 (95% CI, 1.04-1.31)] compared with Whites. In Black infants, the OR for the overall mortality was 1.35 (95% CI, 1.28-1.42), and sepsis-related mortality was 1.20 (95% CI, 1.06-1.35) compared to Whites. Although the prevalence of sepsis is marginally higher in Hispanic infants compared with Whites, the overall and sepsis-related mortalities are the highest in Black infants compared with all races and ethnic groups.

Circ_001653 alleviates sepsis associated-acute kidney injury by recruiting BUD13 to regulate KEAP1/NRF2/HO-1 signaling pathway

BackgroundThe kidney is exceptionally vulnerable during sepsis, often resulting in sepsis-associated acute kidney injury (SA-AKI), a condition that not only escalates morbidity but also significantly raises sepsis-related mortality rates. Circular RNA circ_001653 has been previously reported to be upregulated in the serum of SA-AKI patients, while the role and underlying mechanism of circ_001653 in SA-AKI remains unknown. In this study, we aimed to explore the functional role and the molecular mechanism of circ_001653 in the pathogenesis of SA-AKI.MethodsLPS-stimulated HK-2 cells and ligation and perforation of cecum (CLP)-induced rats were used as in vitro and in vivo models of SA-AKI. The target gene expression levels were measured using qRT-PCR and western blot. Renal function (BUN, sCr, uNGAL, and uKIM-1), and renal pathological changes were detected in septic mice. TUNEL and EdU assays were conducted to measure apoptosis and proliferation rates in vitro. DCFH-DA staining was used to detect ROS levels in vitro and in vivo. Oxidative stress markers (SOD, GSH-Px, MDA, and SOD), and inflammation markers (IL-1β, IL-6, and TNF-α) were determined using commercial kits both in vitro and in vivo. Additionally, gain-and-loss-of-function assays and mechanistic experiments were conducted to explore the regulatory role of circ_001653 in SA-AKI pathogenesis.ResultsData showed that circ_001653 expression was high in LPS-stimulated HK-2 cells and CLP-induced rat renal tissue and was mainly localized in the cytoplasm. Notably, circ_001653 silencing alleviated SA-AKI by reducing apoptosis and alleviating oxidative stress and inflammation in HK-2 cells and renal tissue of rats. Mechanistically, it was found that circ_001653 alleviated SA-AKI by recruiting BUD13 to activate the KEAP1/Nrf2/HO-1 signaling pathway.ConclusionsTo summarize, our study is the first to reveal elevated expression of circ_001653 in sepsis-associated AKI, and its downregulation effectively attenuates AKI by reducing apoptosis, inflammation, and oxidative stress. Mechanistically, circ_001653 exerts its effects by recruiting BUD13 to activate the KEAP1/Nrf2/HO-1 signaling pathway. These findings suggest circ_001653 as a potential therapeutic target for the drug development of sepsis-associated AKI.

Multinational trends in sepsis mortality between 1985 and 2019: a temporal analysis of the WHO Mortality Database

ObjectivesUnderstanding the burden of disease of sepsis is essential for monitoring the effectiveness of international strategies to improve sepsis care. Our objective was to describe the multinational trend of sepsis-related...

Does Gastroesophageal Reflux Disease Increase the Risk of Sepsis and Its 28-day Mortality? A Causal Study Using a Mendelian Randomization Approach.

Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder. Recent studies indicate that GERD may exert systemic effects, potentially elevating the risk of severe infections, including sepsis. Nevertheless, the causal relationship between GERD and sepsis, as well as sepsis-related 28-day mortality, remains uncertain. The aim of this study is to investigate the causal relationship between GERD and the risk of sepsis, including 28-day mortality of sepsis. This study utilized a two-sample Mendelian Randomization (MR) approach to analyze data from publicly available genome-wide association studies (GWAS) databases ( https://gwas.mrcieu.ac.uk/ ). The analysis comprised 129,080 cases and 473,524 controls for GERD; 11,643 patients and 474,841 controls for sepsis; and 1,896 patients and 484,588 controls for 28-day mortality from sepsis. The objective was to evaluate the causal impact of GERD on the risk of sepsis and 28-day sepsis mortality. Genetic variation data pertinent to GERD were obtained from the most recent genome-wide association studies (GWAS). The primary analysis employed the Inverse Variance Weighted (IVW) method. Sensitivity and pleiotropy analyses were performed to validate the robustness of the findings. MR analysis revealed a notable link between genetically predicted GERD and increased sepsis risk (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.24-1.52; p = 2.79 × 10-9). Moreover, GERD correlated with elevated 28-day mortality of sepsis (OR 1.44, 95% CI 1.11-1.85; p = 5.34 × 10-3). These results remained consistent throughout various sensitivity analyses, indicating their resilience against potential pleiotropy and other biases. This study indicates that genetic predisposition to GERD may be linked to an elevated risk of sepsis and its associated 28-day mortality. However, the study does not establish a direct causal relationship for GERD itself, nor does it assess the impact of GERD treatment. Further research is needed to explore the underlying mechanisms and potential therapeutic interventions involved.

Divergent effects of tumor necrosis factor (TNF) in sepsis: a meta-analysis of experimental studies

IntroductionExperimental studies in animals have yielded conflicting results on the role of Tumor Necrosis Factor (TNF) in sepsis and endotoxemia, with some reporting adaptive and others inappropriate effects. A meta-analysis of the available literature was performed to determine the factors explaining this discrepancy.MethodsThe study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol was registered with PROSPERO (CRD42020167384) prior to data collection. PubMed and Embase were the databases queried. Risk of bias was evaluated using the SYRCLE Risk of Bias Tool. All animal studies investigating sepsis-related mortality and modified TNF signaling were considered eligible. The exclusion criteria were: lack of mortality data, 7-day mortality rates below 10% in both wild type and TNF-altered pathway animals, and absence of an English abstract. To determine the role of TNF according to the experimental protocol, three approaches were used: first an approach based on the statistical significance of each experiment, then the pooled mortality was calculated, and finally the weighted risk ratio for mortality was assessed.ResultsA total of 175 studies were included in the analysis, comprising a total of 760 experiments and involving 19,899 animals. The main species used were mice (77%) and rats (21%). The most common method of TNF pathway modulation was TNF pathway inactivation that was primarily associated with an inappropriate secretion of TNF. At the opposite, TNF injection was associated with an adaptive role of TNF. Lipopolysaccharide (LPS) injection was the most used stimulus to establish an infectious model (42%) and was strongly associated with an inappropriate role of TNF. Conversely, live bacterial models, especially the cecal ligation and puncture (CLP) model, pneumonia, meningitis, and gastrointestinal infection, were associated with an adaptive role. This was particularly evident for Listeria monocytogenes, Streptococcus pneumoniae.ConclusionThe role of TNF during infection varies depending on the experimental model used. Models that mimic clinical conditions, based on virulent bacteria that cause high mortality even at low inocula, demonstrated an adaptive role of TNF. Conversely, models based on LPS or low-pathogenic live bacteria, administered at doses well above physiological thresholds and combined with early antibiotic therapy, were associated with an inappropriate role.Graphical abstract

NEWS, NEWS2, and qSOFA accuracy in predicting sepsis-related mortality in acute myeloid leukemia: a retrospective single-center analysis.

Acute myeloid leukemia (AML) treated with intensive chemotherapy carries a high risk of severe infection. The development of reliable assessment tools to promptly identify patients at risk of developing critical illness is essential to prevent delays in intensive care unit (ICU) admission. This study evaluated the accuracy of quick Sequential Organ Failure Assessment (qSOFA) score, National Early Warning Score (NEWS), and NEWS2 score in predicting ICU admission and sepsis-related mortality in this population. A retrospective analysis was conducted, including 365 episodes of febrile neutropenia in 126 patients. The results showed that all three scores-qSOFA, NEWS, and NEWS2-demonstrated good accuracy for all outcomes, with area under the receiver-operating characteristic curve values for sepsis-related mortality of 0.812, 0.858, and 0.848, respectively. In addition, the scores exhibited excellent accuracy in predicting ICU admission and the composite outcome of ICU admission or sepsis-related mortality. To our knowledge, this is the first study to evaluate the accuracy of NEWS in a population of patients with AML who did not undergo stem cell transplantation. These findings suggest that NEWS and NEWS2 are effective tools for identifying patients with AML at high risk of clinical deterioration during febrile neutropenia, supporting their use in clinical practice.

Prophylactic antibiotics in patients with alcohol-associated hepatitis receiving steroids: A systematic review and meta-analysis.

The benefits of prophylactic antibiotics in patients with alcohol-associated hepatitis (AH) receiving steroids remain unclear. We aimed to assess the clinical impact of prophylactic antibiotics in AH patients receiving steroids. We systematically reviewed four electronic databases from inception to 30 November 2023. Pooled estimates were analysed using random-effects models. The primary outcome was 90-day survival. Secondary outcomes included infection at days 30 and 90 days, hepatorenal syndrome (HRS), acute kidney injury (AKI), hepatic encephalopathy (HE) and drug-related adverse events (AE). Trial sequential analyses were performed for the primary outcome of 90-day mortality. We screened 419 articles and included six eligible studies (four RCTs and two matched cohort studies) with a total of 510 patients. Compared to standard medical treatment (SMT), prophylactic antibiotics were associated with a lower risk of infection at 30 days (OR: 0.35, 95%CI: 0.20-0.59, I 2 = 0%), infection at 90 days (OR: 0.26, 95%CI: 0.10-0.67, I 2 = 0%) and a lower rate of HE (OR: 0.32, 95%CI: 0.12-0.87, I 2 = 0%). However, prophylactic antibiotics did not improve 90-day survival, sepsis-related mortality, HRS, or AKI. The risks of drug-related AE and fungal infections were similar in patients with AH who received prophylactic antibiotics or SMT. Using trial sequential analysis, the minimum sample size required to detect a 15% relative risk reduction in 90 days mortality with prophylactic antibiotics was 1171. In hospitalized AH patients receiving steroid therapy, prophylactic antibiotics reduced the risk of infection and HE, but did not improve survival or prevent AKI compared to SMT.

Predictors of Sepsis and Sepsis-related Mortality in Critically Ill Burn Patients: A Single Tertiary Care Center Experience.

Clinical diagnosis of sepsis is challenging, emphasizing the importance of regular bacterial surveillance, and tailored antimicrobial therapy. This study aims to elucidate the predictors of sepsis in critically ill burn patients. A retrospective analysis was conducted on patients admitted to the burn intensive care unit between 2016 and 2022. Demographics, type of burn, total body surface area (TBSA), presence of inhalation injury, mortality, sepsis, deep vein thrombosis, pulmonary embolism, pneumonia, cultures, and laboratory findings were collected. Descriptive statistics and survival analysis were used to analyze trends during the 7-year period. The study encompassed 196 participants. Among patient factors, men constituted 73.4% (n = 102) of those without sepsis and 86.0% (n = 49) with sepsis, with an association between sepsis and lower age (34 versus 41 years) as well as larger TBSA (41.1% versus 17.3%). Inhalation injury was a significant predictor of sepsis [35.1% (n = 20) versus 11.6% (n = 16)]. Mortality was higher in sepsis cases [17.5% (n = 10) versus 2.9% (n = 4)], as well as positive blood cultures [47.4% (n = 27) versus 2.2% (n = 3)], positive wound cultures [71.9% (n = 41) versus 12.2% (n = 17)], and positive fungal cultures [12.3% (n = 7) versus 0% (n = 0)]. Multivariable analysis identified age and TBSA as significant predictors of sepsis (P = 0.025, P < 0.001). Age, TBSA affected emerge as a strong risk factor for sepsis among critically ill burn patients. It underscores the need for vigilant monitoring to improve outcomes and reduce sepsis-related mortality.

Patient and community centered approaches to sepsis among birthing people

Sepsis is the second leading cause of maternal death in the U.S. For racial and ethnic minoritized birthing people, especially those who are Black and living in underserved communities, labor and postpartum are particularly vulnerable risk periods. To reduce sepsis-related morbidity and mortality and promote maternal health equity, community co-led, and co-designed interventions are urgently needed. In this commentary, we introduce the design and goals of our EnCoRe MoMS study as an exemplar for employing community based participatory research principals iteratively throughout the research process and integrated across all study aims. We also highlight our early lessons learned and recommendations for best practices. Our novel model and ongoing work have implications for scaling academic-community research partnerships for other causes of severe maternal morbidity and maternal health equity nationally.

A novel vital sign pattern predicts sepsis-related myocardial injury mortality

Non-invasive, real-time monitorable indicators for early assessment of sepsis-associated myocardial injury (SMI) are still lacking. We aimed to develop non-invasive, real-time indicators for early assessment of SMI using bedside heart rate (HR) and diastolic arterial pressure (DAP) monitors. In this multi-center cohort study, piece-wise exponential additive mixed models were used to estimate the exposure window and time fraction of the hazardous exposure proportion, and secondarily to analyze the exposure characterization on this basis to identify high-risk exposure pattern. In total, 20,043 patients were finally included; we found that SMI patients had the highest survival rate when HR was <90bpm or DAP was between 50 and 70mmHg. Further investigation revealed that the SMI high-risk exposure pattern was the H1D-1 (HR ≥ 90bpm and DAP ≤ 50mmHg, exposure proportion>0.3 and 0.2, respectively, and exposure window on admission day 1). H1D-1 exposure pattern using glucocorticoids significantly increased the risk of mortality in H1D-1. Validation against various methodologies and data sources demonstrated acceptable consistency.

Prognostic Impact of Post-Transplant Diabetes Mellitus in Kidney allograft recipients: A Meta-analysis.

Post-transplant diabetes mellitus (PTDM) is a complex condition arising from various factors including immunosuppressive medications, insulin resistance, impaired insulin secretion, and inflammatory processes. Its impact on patient and graft survival is a significant concern in kidney transplant recipients. PTDM's impact on kidney transplant recipients, including patient and graft survival and cardiovascular mortality, is a significant concern, given conflicting findings in previous studies. This meta-analysis was imperative to not only incorporate emerging evidence but also to delve into cause-specific mortality considerations. We aimed to comprehensively evaluate the association between PTDM and clinical outcomes, including all-cause and cardiovascular mortality, sepsis-related mortality, malignancy-related mortality, and graft loss, in kidney transplant recipients. PubMed, Ovid/Medline, Web of Science, Scopus, and Cochrane Library databases were screened and studies evaluating the effect of PTDM on all-cause mortality, cardiovascular mortality, sepsis-related mortality, malignancy-related mortality, and overall graft loss in adult kidney transplant recipients were included. 53 studies, encompassing a total of 138,917 patients, to evaluate the association between PTDM and clinical outcomes were included. Our analysis revealed a significant increase in all-cause mortality (RR 1.70, 95% CI 1.53 to 1.89, P<0.001) and cardiovascular mortality (RR 1.86, 95% CI 1.36 to 2.54, P<0.001) among individuals with PTDM. Moreover, PTDM was associated with a higher risk of sepsis-related mortality (RR 1.96, 95% CI 1.51 to 2.54, P<0.001) but showed no significant association with malignancy-related mortality (RR 1.20, 95% CI 0.76 to 1.88). Additionally, PTDM was linked to an increased risk of overall graft failure (RR 1.33, 95% CI 1.16 to 1.54, P<0.001). These findings underscore the importance of comprehensive management strategies and the need for research targeting PTDM to improve outcomes in kidney transplant recipients.

IRhom2 deficiency reduces sepsis-induced mortality associated with the attenuation of lung macrophages in mice

Sepsis has a high mortality rate and leads to multi-organ failure, including lung injury. Inactive rhomboid protease family protein (iRhom2) has been identified as accountable for the release of TNF-α, a crucial mediator in the development of sepsis. This study aimed to evaluate the role of iRhom2 in sepsis and sepsis-induced acute lung injury (ALI). TNF-α and IL-6 secretion in vitro by peritoneal macrophages from wild-type (WT) and iRhom2 knoukout (KO) mice was assessed by enzyme-linked immunosorbent assay. Cecal ligation and puncture (CLP)-induced murine sepsis model was used for in vivo experiments. To evaluate the role of iRhom2 deficiency on survival during sepsis, both WT and iRhom2 KO mice were monitored for 8 consecutive days following the CLP. For histologic and biochemical examination, the mice were killed 18 h after CLP. iRhom2 deficiency improved the survival of mice after CLP. iRhom2 deficiency decreased CD68+ macrophage infiltration in lung tissues. Multiplex immunohistochemistry revealed that the proportion of Ki-67+ CD68+ macrophages was significantly lower in iRhom2 KO mice than that in WT mice after CLP. Moreover, CLP-induced release of TNF-α and IL-6 in the serum were significantly inhibited by iRhom2 deficiency. iRhom2 deficiency reduced NF-kB p65 and IκBα phosphorylation after CLP. iRhom2 deficiency reduces sepsis-related mortality associated with attenuated macrophage infiltration and proliferation in early lung injury. iRhom2 may play a pivotal role in the pathogenesis of sepsis and early stage of sepsis-induced ALI. Thus, iRhom2 may be a potential therapeutic target for the management of sepsis and sepsis-induced ALI.

Cost-effectiveness of treating childhood acute myeloid leukemia at a tertiary care center in North India.

Childhood cancers are a significant global health concern, particularly in low- and middle-income countries (LMICs), where over 80% of childhood cancer patients reside. In India, acute myeloid leukemia (AML) constitutes a significant portion of childhood cancers; however, the data on the cost-effectiveness of childhood AML treatment in India and other LMICs remain limited. The study focused on children (<15years of age) diagnosed with AML at a tertiary care cancer center in North India. Data, including treatment outcome, treatment-related morbidity, mortality, and costs were retrospectively collected from the electronic medical record and hospital database. Cost-effectiveness was assessed using disability-adjusted life years (DALY) averted in relation to the country-specific cost-effectiveness threshold. Among 59 AML patients, treatment-related high mortality rates, abandonment, and limited access to bone marrow transplantation were notable challenges. Intensive chemotherapy resulted in substantial sepsis-related complications, with treatment-related mortality reaching 30%. The 3-year event-free survival and overall survival of the 43 patients who received intensive therapy were 24.5%±7.6% and 27.9%±8.3%, respectively. Despite these challenges, treating childhood AML was still found to be cost-effective. The total cost per newly diagnosed patient treated with curative intent was $4454. Cost per DALY averted accounted for 24% of the gross domestic product (GDP) per capita, rendering the treatment to be cost-effective with a stringent cost-effectiveness threshold utilized. The study underscores the challenges faced while treating childhood AML in LMICs, including treatment-induced high sepsis-related mortality and abandonment. Despite these challenges, it remains cost-effective to treat childhood AML in India. Future efforts should focus on reducing treatment-related morbidity and mortality to further improve outcomes and cost-effectiveness.

Diagnostic Accuracy of Clinical Sign Algorithms to Identify Sepsis in Young Infants Aged 0 to 59 Days: A Systematic Review and Meta-analysis.

Accurate identification of possible sepsis in young infants is needed to effectively manage and reduce sepsis-related morbidity and mortality. Synthesize evidence on the diagnostic accuracy of clinical sign algorithms to identify young infants (aged 0-59 days) with suspected sepsis. MEDLINE, Embase, CINAHL, Global Index Medicus, and Cochrane CENTRAL Registry of Trials. Studies reporting diagnostic accuracy measures of algorithms including infant clinical signs to identify young infants with suspected sepsis. We used Cochrane methods for study screening, data extraction, risk of bias assessment, and determining certainty of evidence using Grading of Recommendations Assessment Development and Evaluation. We included 19 studies (12 Integrated Management of Childhood Illness [IMCI] and 7 non-IMCI studies). The current World Health Organization (WHO) 7-sign IMCI algorithm had a sensitivity of 79% (95% CI 77%-82%) and specificity of 77% (95% CI 76%-78%) for identifying sick infants aged 0-59 days requiring hospitalization/antibiotics (1 study, N = 8889). Any IMCI algorithm had a pooled sensitivity of 84% (95% CI 75%-90%) and specificity of 80% (95% CI 64%-90%) for identifying suspected sepsis (11 studies, N = 15523). When restricting the reference standard to laboratory-supported sepsis, any IMCI algorithm had a pooled sensitivity of 86% (95% CI 82%-90%) and lower specificity of 61% (95% CI 49%-72%) (6 studies, N = 14278). Heterogeneity of algorithms and reference standards limited the evidence. IMCI algorithms had acceptable sensitivity for identifying young infants with suspected sepsis. Specificity was lower using a reference standard of laboratory-supported sepsis diagnosis.

Development and validation of a nomogram model for predicting 28-day mortality in patients with sepsis

BackgroundThis study aimed to develop and validate a nomogram model for predicting 28-day mortality in patients with sepsis in the intensive care unit (ICU). MethodsWe retrospectively analyzed data from 331 patients with sepsis admitted to the ICU as a training set and collected a validation set of 120 patients. Both groups were followed for 28 days. Logistic regression analyses were performed to identify the potential prognostic factors for sepsis-related 28-day mortality. A nomogram model was generated to predict 28-day mortality in patients with sepsis in the ICU. Receiver operating characteristic (ROC) curve analysis, calibration curves, and decision curve analysis (DCA) were used to evaluate the model's prediction performance and clinical application. In addition, we used ROC curve analysis and DCA to compare this model with the sequential organ failure assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores and further assessed the clinical value of our model. ResultsLogistic multivariate regression analysis revealed that mechanical ventilation, oxygenation index, and lactate and blood urea nitrogen (BUN) levels were independent predictors of 28-day mortality in patients with sepsis in the ICU. We developed a nomogram model based on these results to further predict 28-day mortality. The model demonstrated satisfactory calibration curves for both training and validation sets. Additionally, in the training set, the area under the ROC curve (AUC) for this model was 0.80. In the validation set, the AUC was 0.82. DCA showed that the high-risk thresholds ranged between 0 and 0.86 in the training set and between 0 and 0.75 in the validation set. We compared the ROC curve and DCA of this model with those of SOFA and APACHE II scores in both the training and validation sets. In the training set, the AUC of this model was significantly higher than those of the SOFA (P = 0.032) and APACHE II (P = 0.004) scores. Although the validation set showed a similar trend, the differences were not statistically significant for the SOFA (P = 0.273) and APACHE II (P = 0.320) scores. Additionally, the DCA showed comparable clinical utility in all three assessments. ConclusionThe present study used four common clinical variables, including mechanical ventilation, oxygenation index and lactate and BUN levels, to develop a nomogram model to predict 28-day mortality in patients with sepsis in the ICU. Our model demonstrated robust prediction performance and clinical application after validation and comparison.

Aqueous extract of Descuraniae Semen attenuates lipopolysaccharide-induced inflammation by inhibiting ER stress and WNK4-SPAK-NKCC1 pathway.

Sepsis causes systemic inflammatory responses and acute lung injury (ALI). Despite modern treatments, sepsis-related ALI mortality remains high. Aqueous extract of Descuraniae Semen (AEDS) exerts anti-endoplasmic reticulum (ER) stress, antioxidant and anti-inflammatory effects. AEDS alleviates inflammation and oedema in ALI. Sodium-potassium-chloride co-transporter isoform 1 (NKCC1) is essential for regulating alveolar fluid and is important in ALI. The NKCC1 activity is regulated by upstream with-no-lysine kinase-4 (WNK4) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). This study aimed to investigate the effects of AEDS on lipopolysaccharide (LPS)-induced ALI model in A549 cells, considering the regulation of ER stress, WNK4-SPAK-NKCC1 cascades, inflammation and apoptosis. Cell viability was investigated by the CCK-8 assay. The expressions of the proteins were assessed by immunoblotting analysis assays. The levels of pro-inflammatory cytokines were determined by ELISA. The expression of cytoplasmic Ca2+ in A549 cells was determined using Fluo-4 AM. AEDS attenuates LPS-induced inflammation, which is associated with increased pro-inflammatory cytokine expression and activation of the WNK4-SPAK-NKCC1 pathway. AEDS inhibits the WNK4-SPAK-NKCC1 pathway by regulating of Bcl-2, IP3R and intracellular Ca2+. WNK4 expression levels are significantly higher in the WNK4-overexpressed transfected A549 cells and significantly decrease after AEDS treatment. AEDS attenuates LPS-induced inflammation by inhibiting the WNK4-SPAK-NKCC1 cascade. Therefore, AEDS is regarded as a potential therapeutic agent for ALI.

Engineered extracellular vesicles coated with an antimicrobial peptide for advanced control of bacterial sepsis.

Alarming sepsis-related mortality rates present significant challenges to healthcare services globally. Despite advances made in the field, there is still an urgent need to develop innovative approaches that could improve survival rates and reduce the overall cost of treatment for sepsis patients. Therefore, this study aimed to develop a novel multifunctional therapeutic agent for advanced control of bacterial sepsis. Extracellular vesicles (EVs) isolated from lipopolysaccharide (LPS) induced HepG2 (hepatocellular carcinoma cells) (iEV) displayed an average particle size of 171.63±2.77nm, a poly dispersion index (PDI) of 0.32±0.0, and a zeta potential (ZP) of -11.87±0.18mV. Compared to HepG2 EV, LPS induction significantly increases the EV protein concentration, PDI and ZP, reduces the average size and promotes cell proliferation and cytoprotective effects of the isolated EVs (iEVs) against LPS-induced cytotoxicity. Coating of iEV with a cationic antimicrobial peptide (AMP) to form PC-iEV slightly changed their physical properties and shifted their surface charge toward neutral values. This modification improved the antibacterial activity (2-fold lower minimum bactericidal concentration [MBC] values) and biocompatibility of the conjugated peptide while maintaining iEV cytoprotective and anti-inflammatory activities. Our findings indicate the superior anti-inflammatory and antibacterial dual activity of PC-iEV against pathogens associated with sepsis.

Procalcitonin and qSOFA as a Marker of Mortality in Sepsis.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The qSOFA and procalcitonin are currently used for both diagnostic as well as prognostic purposes. To explore the combined use of day one procalcitonin level and qSOFA scores for prognostication of sepsis-related mortality. This was a prospective observational study. All patients who fulfilled the inclusion criteria for sepsis with an age of more than 16 years were enrolled in the study. In this study of 211 patients, 15 patients died (7.1%) during hospital stay. Among the 15 patients who died, the highest mortality of 29.4% was seen in patients with qSOFA of "3", qSOFA of "2" had a mortality of 12.8%, qSOFA of "1" had a mortality of 1% and qSOFA of "0" had zero mortality. In this study, procalcitonin had a statistically significant positive correlation/association with both qSOFA and mortality. The qSOFA and procalcitonin at presentation to the emergency department in septic patients have a significant correlation with mortality in patients hospitalized with sepsis. Obtaining these two parameters at presentation will help in managing aggressively these patients who at presentation have higher qSOFA and procalcitonin levels.