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Sepsis is a potentially fatal condition arising from an abnormal immune response to an infection, which can result in organ failure and even death. To explore the mechanism underlying the dysregulated immune response during sepsis and identify potential therapeutic targets, single-cell RNA sequencing (scRNA-seq) and immune repertoire analysis were conducted to depict the cellular landscape of peripheral blood cells in septic mice. We observed significant alterations in the number and proportion of peripheral blood cell populations driven by sepsis. By combining single-cell gene expression profiles and B cell receptor (BCR) repertoire analysis, we discerned that infection inflicted serious damage on the antigen presentation ability of B cells and the diversity of BCR in a short time. In addition, we found that the cecal ligation and puncture procedure in mice inhibited the communication signals of CD4 + and CD8 + T cells and decreased the interactions between B cells and other cells. Our study provides detailed insights into the dynamic changes in the biological characteristics of peripheral blood cells driven by sepsis and provides important advances in our understanding of immune disorders during sepsis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgments We gratefully acknowledge the participation of Shanghai OE Biotech Co., Ltd for the support of construction of single cell sequencing Library, and thanks Mr. Zhengshan Chen (Laboratory of Advanced Biotechnology) for the support of data analysis and visualization. This study was supported by grants from the National Natural Science Foundation of China (82170229)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sepsis continues to be a major cause of death and illness globally, posing significant challenges for healthcare professionals. In the pursuit of more accurate and timely monitoring tools, the concept of capnodynamically derived mixed venous oxygen saturation (Capno-SvO 2 ) has emerged as a promising method. Capno-SvO 2 provides a non-invasive way to assess and track SvO 2 and could serve as an additional tool alongside more invasive methods like the pulmonary artery catheter. This could potentially be of great value in the care of critically ill patients with sepsis, where alternative minimal invasive monitoring methods may vary in reliability. The aim of the current study was to compare capno-SvO 2 against values obtained through pulmonary artery blood sample CO-oximetry and continuous fiberoptic SvO 2 monitoring, using a well-established porcine experimental sepsis model. Anesthetized pigs were exposed to a standardized endotoxin infusion sepsis protocol, followed by a series of maneuvers typically applied in sepsis care. Simultaneous recordings were done throughout the experiment for all three monitoring methods. Bland-Altman analysis corrected for repeated measurements was used to assess the agreement of absolute values between the paired recording of CO-oximetry and Capno-SvO 2 as well as between CO-oximetry and fiberoptic SvO 2 . The ability of Capno-SvO 2 and fiberoptic SvO2 to track changes was assessed by concordance rate. A total of 10 animals and 275 paired datapoints were included in the study. The majority of the animals displayed pronounced hemodynamical instability in response to endotoxin exposure and subsequent treatment interventions. Analysis of all paired data points showed a bias between Capno-SvO 2 and CO-oximetry SvO 2 of + 1% with 95% limits of agreement of -14% to + 17%. The corresponding numbers for fiberoptic SvO 2 and CO-oximetry SvO 2 were -4% and -15% to + 8%. The concordance rate as compared to CO-oximetry, were 97% and 93% for Capno-SvO 2 and fiberoptic SvO 2 , respectively. In this experimental sepsis model, continuous, non-invasive Capno-SvO 2 generates average absolute values comparable to the gold standard CO-oximetry albeit with relatively wide limits of agreement. Capno-SvO 2 displayed a concordance rate of 97% against CO-oximetry and exhibits better trending ability compared to invasive fiberoptic SvO 2 ., (© 2024. The Author(s).)

Objective: To establish a model that can predict the risk of requiring mechanical ventilation within 48 h after admission in patients with sepsis., Methods: Data for patients with sepsis admitted to Dongyang People's Hospital from October 2011 to October 2023 were collected and divided into a modeling group and a validation group. Independent risk factors in the modeling group were analyzed, and a corresponding predictive nomogram was established. The model was evaluated for discriminative power (the area under the curve of the receiver operating characteristic curve, AUC), calibration degree (Hosmer-Lemeshow test), and clinical benefit (decision curve analysis, DCA). Models based on the Sequential Organ Failure Assessment (SOFA) scores, the National Early Warning Score (NEWS) scores and multiple machine learning methods were also established., Results: The independent factors related to the risk of requiring mechanical ventilation in patients with sepsis within 48 h included lactic acid, pro-brain natriuretic peptide (PRO-BNP), and albumin levels, as well as prothrombin time, the presence of lung infection, and D-dimer levels. The AUC values of nomogram model in the modeling group and validation group were 0.820 and 0.837, respectively. The nomogram model had a good fit and clinical value. The AUC values of the models constructed using SOFA scores and NEWSs were significantly lower than those of the nomogram ( P < 0.01). The AUC value of the integrated machine-learning model for the validation group was 0.849, comparable to that of the nomogram model ( P = 0.791)., Conclusion: The established nomogram could effectively predict the risk of requiring mechanical ventilation within 48 h of admission by patients with sepsis. Thus, the model can be used for the treatment and management of sepsis., Competing Interests: The authors declare that they have no competing interests., (© 2024 Wang et al.)

Translocator protein 18 kDa (TSPO) is a mitochondrial membrane protein that is involved in inflammation, oxidative stress, and steroidogenesis. TSPO may be a marker of inflammatory responses in the brain and other organs, but there have been few studies of the potential clinical significance of measuring the circulating TSPO concentration, especially in patients with sepsis. In this study, we compared the circulating TSPO concentrations of patients with sepsis and healthy controls to investigate the utility of plasma TSPO for the diagnosis of sepsis. Patients with sepsis admitted to the intensive care unit of Hiroshima University Hospital between January 2020 and April 2024 were enrolled. Plasma samples were collected from patients within 24 hours of admission and also from healthy volunteers, and their plasma TSPO concentrations were compared. Receiver operating characteristic analysis was used to evaluate the usefulness of plasma TSPO concentration for the diagnosis of sepsis. We also investigated the relationships of TSPO concentration with the severity of sepsis, complications, and prognosis of the patients. Eighty subjects (52 patients and 28 controls) were included in this study. The plasma TSPO concentrations of the patients with sepsis were significantly lower than those of the healthy controls (0.094 vs 0.25 ng/mL, P < .001), and receiver operating characteristic analysis generated an area under the curve of 0.81 (95% confidence interval: 0.72-0.91). In patients with sepsis, the TSPO concentration was not associated with the severity of sepsis, complications, or prognosis. Plasma TSPO may be a useful biomarker for the diagnosis of sepsis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Sepsis presents a significant healthcare challenge, characterized by high morbidity and mortality rates. There is a scarcity of relevant studies investigating the association between serum lactate dehydrogenase level and the prognosis of sepsis in patients from intensive care unit, with smaller sample sizes compared to other studies., Methods: A retrospective analysis was conducted utilizing data from the Second Affiliated Hospital of Guangzhou Medical University and the Medical Information Mart for Intensive Care IV (MIMIC-IV). The primary outcome was the in-hospital mortality. Multivariate Cox proportional hazards regression was adopted to assess the independent association. Receiver operator characteristic (ROC) curve was used to evaluate the predictive value., Results: We included a total of 2148 patients in the Guangzhou Sepsis Cohort (GZSC) database and 5830 patients in the MIMIC-IV database. In multivariate Cox proportional hazards regression, high levels of LDH are significantly associated with higher mortality (HR = 1.21, 95% CI 1.13-1.30, p < 0.001 in the GZSC database and HR = 1.19, 95% CI 1.13-1.25, p < 0.001 in the MIMIC-IV database). The ROC curves showed that the AUC of LDH was 0.663 in the GZSC database and 0.660 in the MIMIC-IV database., Conclusions: A lower lactate dehydrogenase level is associated with reduced in-hospital mortality among patients with sepsis, suggesting its potential as a valuable marker for predicting prognosis in this patient population., (© 2024. The Author(s).)

Objective: To investigate the metabolomic profiles associated with different immune activation states in sepsis patients., Design: Subgroup analysis of the PROVIDE (a Personalized Randomized trial of Validation and restoration of Immune Dysfunction in severe infections and Sepsis) prospective clinical study., Setting: Results of the PROVIDE study showed that patients with sepsis may be classified into three states of immune activation: 1) macrophage-activation-like syndrome (MALS) characterized by hyperinflammation, sepsis-induced immunoparalysis, and 3) unclassified or intermediate patients without severe immune dysregulation., Patients or Subjects: Two hundred ten patients from 14 clinical sites in Greece meeting the Sepsis-3 definitions with lung infection, acute cholangitis, or primary bacteremia., Interventions: During our comparison, we did not perform any intervention., Measurements and Main Results: Untargeted metabolomics analysis was performed on plasma samples from 210 patients (a total of 1394 products). Differential abundance analysis identified 221 significantly different metabolites across the immune states. Metabolites were enriched in pathways related to ubiquinone biosynthesis, tyrosine metabolism, and tryptophan metabolism when comparing MALS to immunoparalysis and unclassified patients. When comparing MALS to unclassified, 312 significantly different metabolites were found, and pathway analysis indicated enrichment in multiple pathways. Comparing immunoparalysis to unclassified patients revealed only two differentially regulated metabolites., Conclusions: Findings suggest distinct metabolic dysregulation patterns associated with different immune dysfunctions in sepsis: the strongest metabolic dysregulation is associated with MALS., Competing Interests: Dr. Dalekos is an advisor or lecturer for Pfizer, Roche, Sanofi, and Sobi and he received research grants from Gilead and has served as principal investigator in studies for Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics Inc, Tiziana Life Sciences, Bayer, Astellas, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics Inc., Sobi, and Intercept Pharmaceuticals. Dr. Netea is supported by an European Research Council Advanced Grant (number 833247) and a Spinoza grant from the Netherlands Organization for Scientific Research. He is a scientific founder of TTxD, Lemba, and Biotrip and he has received independent educational grants from TTxD, GSK, Ono Pharma, and ViiV Healthcare. Dr. Giamarellos-Bourboulis has received honoraria from Abbott Products Operations, bioMérieux, ThermoFisherBrahms GmbH, GSK, InflaRx GmbH, Sobi, and XBiotech Inc; independent educational grants from Abbott Products Operations, AbbVie, bioMérieux Inc, Johnson & Johnson, MSD, Novartis, Sobi, and UCB; and funding from the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), the Horizon 2020 European Grants ImmunoSep and RISCinCOVID (granted to the Hellenic Institute for the Study of Sepsis), and the Horizon Health European Grant EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis). Dr. Kranidioti’s institutions received funding from The Hellenic Institute for the Study of Sepsis, bioMerieux, and Spinoza grant of the Netherlands Organization for Scientific Research. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: Sepsis-induced coagulopathy (SIC) is a severe complication of sepsis, characterized by poor prognosis and high mortality. However, the predictors of SIC in pediatric patients have yet to be identified. Our aim was to develop a user-friendly and efficient nomogram for predicting SIC in sepsis patients admitted to the pediatric intensive care unit (PICU)., Materials and Methods: We screened 948 sepsis patients admitted to the PICU in three hospitals located in Shandong, China. Least absolute shrinkage and selector operation (LASSO) regression was used in the training cohort for variable selection and regularization. The selected variables were utilized to construct a nomogram for predicting the risk of SIC among sepsis patients admitted to the PICU., Results: Overall, SIC was observed in 324 (40.3 %) patients. The morbidity of SIC in sepsis patients is associated with age, fibrinogen, prothrombin time, C-reactive protein, lactate and the pediatric sequential organ failure assessment score. We developed a nomogram for the early identification of SIC in the training cohort (area under the curve [AUC] 0.869, 95 % confidence interval [CI] 0.830-0.907, sensitivity 75.7 %, specificity 84.8 %) and validation cohorts (validation cohort 1: AUC 0.854, 95 % CI 0.805-0.903, sensitivity 72.0 %, specificity 86.9 %; validation cohort 2: AUC 0.853, 95 % CI 0.796-0.910, sensitivity 70.1 %, specificity 87.8 %). The calibration plots of the nomogram demonstrated a high level of concordance in the SIC probabilities between the observed and predicted values., Conclusions: The novel nomogram showed excellent predictive performance for the morbidity of SIC among sepsis patients admitted to the PICU, potentially assisting healthcare professionals in early identification and intervention for SIC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Neutropenic sepsis (NS) is one of the leading causes of death among patients with hematologic malignancies. Identifying its predictive factors is fundamental for early detection. Few studies have evaluated the predictive factors in relation to microbial infection confirmation, which is clinically important for initiating sepsis treatment. This study aimed to determine whether selected biomarkers (i.e., body temperature, C-reactive protein, albumin, procalcitonin), treatment-related characteristics (i.e., diagnosis, duration of neutropenia, treatment modality), and infection-related characteristics (i.e., infection source, causative organisms) can predict NS in patients with hematologic malignancies. We also aimed to identify the optimal predictive cutoff points for these parameters. This retrospective case-control study used the data from a total of 163 patients (58 in the sepsis group and 105 in the non-sepsis group). We collected data with reference to the day of specimen collection, with which microbial infection was confirmed. Multiple logistic regression was used to determine predictive risk factors and the area under the curve (AUC) of the receiver operating characteristic for the optimal predictive cutoff points. The independent predictors of NS were average body temperature during a fever episode and procalcitonin level. The odds for NS rose by 9.97 times with every 1°C rise in average body temperature (95% confidence interval, CI [1.33, 75.05]) and by 2.09 times with every 1 ng/mL rise in the procalcitonin level (95% CI [1.08, 4.04]). Average body temperature (AUC = 0.77, 95% CI [0.68, 0.87]) and procalcitonin levels (AUC = 0.71, 95% CI [0.59, 0.84]) have fair accuracy for predicting NS, with the optimal cutoff points of 37.9°C and 0.55 ng/mL, respectively. This study found that average body temperature during a fever episode and procalcitonin are useful in predicting NS. Thus, nurses should carefully monitor body temperature and procalcitonin levels in patients with hematologic malignancies to detect the onset of NS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The study aimed to investigate the clinical significance of serum cytokine-induced apoptosis inhibitor 1 (CIAPIN1) and its potential impact on cardiac dysfunction and inflammatory response induced by sepsis. A cross-sectional study was conducted in an intensive care unit (ICU) involving 80 healthy individuals and 95 severe sepsis patients. The data were analyzed to establish the correlation between CIAPIN1 levels and the onset of cardiac dysfunction in patients with sepsis. The associations have been established by the Pearson correlation test, one-way ANOVA, Bonferroni post hoc test, and plotting the receiver operating characteristic (ROC). H9c2 cells were treated with LPS (1 μg/mL) for 24 h to establish an in vitro model of septic cardiomyopathy. Meanwhile, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA). Serum CIAPIN1 levels were considerably lower in sepsis patients with cardiac dysfunction. CIAPIN1 expression levels were negatively correlated with TNF-α (r = -0.476, P<0.001), IL-1β (r = -0.584, P<0.001), IL-6 (r = -0.618, P<0.001), creatine kinase- MB (CK-MB) (r = -0.454, P<0.001), and high-sensitive cardiac troponin T (hs-cTnT) (r = -0.586, P<0.001). The ROC curve showed that CIAPIN1 significantly identify sepsis patients from healthy individuals. CIAPIN1 knockdown decreases cardiomyocyte proliferation and increases apoptosis induced by LPS. In addition, CIAPIN1 knockdown reduced cardiac dysfunction and increased inflammatory response in H9c2 rat cardiomyocytes. CIAPIN1 could be a potential biomarker for detecting sepsis patients and suppressing CIAPIN1 expression in H9c2 rat cardiomyocytes, attenuating sepsis-induced cardiac dysfunction., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Lin Chen reports was provided by Shanghai Pudong New Area Zhoupu Hospital (Shanghai Health Medical College Affiliated Zhoupu Hospital). Dr. Lin Chen reports a relationship with Shanghai Pudong New Area Zhoupu Hospital (Shanghai Health Medical College Affiliated Zhoupu Hospital) that includes: employment. Dr. Lin Chen has patent pending to N/A. N/A If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background:  Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) criteria were launched nearly 20 years ago. Following the revised conceptual definition of sepsis and subsequent omission of systemic inflammatory response syndrome (SIRS) score from the latest sepsis diagnostic criteria, we omitted the SIRS score and proposed a modified version of JAAM DIC criteria, the JAAM-2 DIC criteria., Objectives:  To validate and compare performance between new JAAM-2 DIC criteria and conventional JAAM DIC criteria for sepsis., Methods:  We used three datasets containing adult sepsis patients from a multicenter nationwide Japanese cohort study (J-septic DIC, FORECAST, and SPICE-ICU registries). JAAM-2 DIC criteria omitted the SIRS score and set the cutoff value at ≥3 points. Receiver operating characteristic (ROC) analyses were performed between the two DIC criteria to evaluate prognostic value. Associations between in-hospital mortality and anticoagulant therapy according to DIC status were analyzed using propensity score weighting to compare significance of the criteria in determining introduction of anticoagulants against sepsis., Results:  Final study cohorts of the datasets included 2,154, 1,065, and 608 sepsis patients, respectively. ROC analysis revealed that curves for both JAAM and JAAM-2 DIC criteria as predictors of in-hospital mortality were almost consistent. Survival curves for the anticoagulant and control groups in the propensity score-weighted prediction model diagnosed using the two criteria were also almost entirely consistent., Conclusion:  JAAM-2 DIC criteria were equivalent to JAAM DIC criteria regarding prognostic and diagnostic values for initiating anticoagulation. The newly proposed JAAM-2 DIC criteria could be potentially alternative criteria for sepsis management., Competing Interests: K.Y. reported receiving grants from Asahi Kasei Pharma and Japan Blood Products Organization. T.I. participated on advisory boards of Japan Blood Products Organization, Asahi Kasei Pharmaceuticals, and Toray Medical. None of the other authors have any potential conflicts of interest to disclose., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: The peripheral perfusion index (PI) reflects microcirculatory blood flow perfusion and indicates the severity and prognosis of sepsis. Method: The cohort comprised 208 patients admitted to the intensive care unit (ICU) with infection, among which 117 had sepsis. Demographics, medication history, ICU variables, and laboratory indexes were collected. Primary endpoints were in-hospital mortality and 28-day mortality. Secondary endpoints included organ function variables (coagulation function, liver function, renal function, and myocardial injury), lactate concentration, mechanical ventilation time, and length of ICU stay. Univariate and multivariate analyses were conducted to assess the associations between the PI and clinical outcomes. Sensitivity analyses were performed to explore the associations between the PI and organ functions in the sepsis and nonsepsis groups. Result: The PI was negatively associated with in-hospital mortality (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.15 to 0.55), but was not associated with 28-day mortality. The PI was negatively associated with the coagulation markers prothrombin time (PT) (β -0.36, 95% CI -0.59 to 0.13) and activated partial thromboplastin time (APTT) (β -1.08, 95% CI -1.86 to 0.31), and the myocardial injury marker cardiac troponin I (cTnI) (β -2085.48, 95% CI -3892.35 to 278.61) in univariate analysis, and with the PT (β -0.36, 95% CI -0.60 to 0.13) in multivariate analysis. The PI was negatively associated with the lactate concentration (β -0.57, 95% CI -0.95 to 0.19), mechanical ventilation time (β -23.11, 95% CI -36.54 to 9.69), and length of ICU stay (β -1.28, 95% CI -2.01 to 0.55). Sensitivity analyses showed that the PI was significantly associated with coagulation markers (PT and APTT) and a myocardial injury marker (cTnI) in patients with sepsis, suggesting that the associations between the PI and organ function were stronger in the sepsis group than the nonsepsis group. Conclusion: The PI provides new insights for assessing the disease severity, short-term prognosis, and organ function damage in ICU patients with sepsis, laying a theoretical foundation for future research., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Despite the fact that red blood cell (RBC) transfusion is commonly applied in surgical intensive care unit (ICU), the effect of RBC transfusion on long-term outcomes remains undetermined. We aimed to explore the association between RBC transfusion and the long-term prognosis of surgical sepsis survivors., Methods: This retrospective study was conducted on adult sepsis patients admitted to a tertiary surgical ICU center in China. Patients were divided into transfusion and non-transfusion groups based on the presence of RBC transfusion. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW)were performed to balance the potential confounders., Results: A total of 1421 surgical sepsis survivors were enrolled, including 403 transfused patients and 1018 non-transfused patients. There was a significant difference in 1-year mortality between the two groups (23.1 ​% vs 12.7 ​%, HR: 1.539, 95 ​% confidence interval [CI]: 1.030-2.299, P ​< ​0.001). After PSM and IPTW, transfused patients still showed significantly increased 1-year mortality risks compared to non-transfused individuals (PSM: 23.6 ​% vs 15.9 ​%, HR 1.606, 95 ​% CI 1.036-2.488 ​P ​= ​0.034; IPTW: 20.1 ​% vs 12.9 ​%, HR 1.600, 95 ​% CI 1.040-2.462 ​P ​= ​0.032). Among patients with nadir hemoglobin below 70 ​g/L, 1-year mortality risks in both groups were similar (HR 1.461, 95 ​% CI 0.909-2.348, P ​= ​0.118). However, among patients with nadir hemoglobin above 70 ​g/L, RBC transfusion was correlated with increased 1-year mortality risk (HR 1.556, 95 ​% CI 1.020-2.374, P ​= ​0.040)., Conclusion: For surgical sepsis survivors, RBC transfusion during ICU stay was associated with increased 1-year mortality, especially when patients show hemoglobin levels above 70 ​g/L., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Information on the comparison of blood microbiota between human immunodeficiency virus (HIV)-infected and HIV-uninfected patients with suspected sepsis by metagenomic next-generation sequencing (mNGS) is limited., Methods: Retrospectively analysis was conducted in HIV-infected and HIV-uninfected patients with suspected sepsis at Changsha First Hospital (China) from March 2019 to August 2022. Patients who underwent blood mNGS testing were enrolled. The blood microbiota detected by mNGS were analyzed., Results: A total of 233 patients with suspected sepsis who performed blood mNGS were recruited in this study, including 79 HIV-infected and 154 HIV-uninfected patients. Compared with HIV-uninfected patients, the proportions of mycobacterium (p = 0.001), fungus (p < 0.001) and viruses (p < 0.001) were significantly higher, while the proportion of bacteria (p = 0.001) was significantly lower in HIV-infected patients. The higher positive rates of non-tuberculous mycobacteriosis (NTM, p = 0.022), Pneumocystis jirovecii (P. jirovecii) (p = 0.014), Talaromyces marneffei (T. marneffei) (p < 0.001) and cytomegalovirus (CMV) (p < 0.001) were observed in HIV-infected patients, compared with HIV-uninfected patients. In addition, compared with HIV-uninfected patients, the constituent ratio of T. marneffei (p < 0.001) in the fungus spectrum were significantly higher, while the constituent ratios of Candida (p < 0.001) and Aspergillus (p = 0.001) were significantly lower in HIV-infected patients., Conclusions: Significant differences in the blood microbiota profiles exist between HIV-infected and HIV-uninfected patients with suspected sepsis., (© 2024. The Author(s).)

Background: Timely recognition of sepsis in emergency department (ED) is challenging. We evaluated the impact of implementing the biomarker monocyte distribution width (MDW) at bedside, on the time to anti-infective administration., Methods: We conducted a before-and-after cohort study in the ED of an academic hospital in Paris, to compare sepsis patients care and outcomes, before and after the implementation of point of care (POC) MDW measurement in the ED. During post-implementation period (period-2), MDW was measured with complete blood count by ED nurses with results given in 2 min: if above 21.5 units, ED physicians were asked to consider sepsis and to start an anti-infectious as soon as possible. Primary endpoint was time to anti-infectious administration (TTA) from ED arrival, and secondary endpoints were TTA from sepsis onset (TTAS), length of stay, mortality, and hospitalization rates., Results: In total, 255 patients (period-1) and 180 patients (period-2) with sepsis were included. The TTA was 5.4 h (3.5-7.7) period-1 and 4.9 h (IQR 2.5-7.1) in period-2 (p = 0.06). MDW implementation significantly reduced the median TTAS from to 3.7 h (IQR 1.5-5.8) in period-1, to 2.2 h (IQR 0.5-4.5) in period-2 (p < 0.001). Mortality rates remained similar between the two periods (18% vs. 16% respectively, p = 0.4), as did hospitalization rates (93% vs. 91%, p = 0.4) and ED length of stay (7.2 h (5.3-9.8) vs 7.0 (5.4-9.4), p = 0.7)., Conclusion: Implementing POC MDW measurement in the ED protocols enhances the timeliness of anti-infective administration from sepsis onset, meeting current sepsis management guidelines., (© 2024. The Author(s).)

Background: Sepsis is a common admission diagnosis in the intensive care unit (ICU). The Sepsis-3 consensus associates sepsis diagnosis with acute organ dysfunction. In these patients troponin elevation is a well-established phenomenon, but its clinical significance is not settled, as no systematic review has addressed the prognostic significance of the increasingly prevalent high-sensitivity troponin assays in acute organ dysfunction setting. This study aims to clarify the association between early serum troponin levels in high-sensitivity assays with short-term mortality risk in septic patients with acute organ dysfunction., Methods: We will systematically search PubMed, Scopus and Embase for original articles; additionally, a manual search will be carried out through relevant literature. Generally, studies will be deemed eligible for inclusion if they evaluate the association between high-sensitivity troponin in the first 24 hours of admission and ICU, 30-days, or In-hospital mortality; in patients with septic shock or sepsis related to acute organ dysfunction. Two reviewers will independently select studies and extract the data. A meta-analysis for mortality outcome will be performed for comparative data regarding two effect measures: Odd ratios and Standardized Mean differences., Discussion: This study will provide further evidence about the role of high-sensitivity troponin assays in predicting mortality in septic patients; potentially helping to guide further research and yielding valuable information for patient assessment. Conclusion about the certainty of evidence will be presented in a ´Summary of findings´ table., Trial Registration: PROSPERO registration: (CRD42024468883)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ferrière-Steinert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Sepsis, a severe inflammatory response to infection, is a global health priority due to its high mortality and long-term disability rates. Its pathophysiology involves both inflammation and immune suppression. Managing sepsis requires significant healthcare resources and expenditure, with sepsis being a leading cause of hospital costs. Gut microbiotas play a crucial role in sepsis, and probiotics show promise in managing it by restoring microbial balance. Despite advances, targeted therapies for sepsis remain elusive, necessitating innovative approaches such as probiotic therapy., Method: Fifty-four eligible patients with sepsis will be randomly assigned to either the synbiotic or placebo group. The synbiotic supplement, KidiLact, comprises ten probiotic strains and prebiotic fructooligosaccharides. Participants will receive two sachets daily for 7 days, mixed with sterile water and administered orally or via gavage. Inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) will be evaluated. Anthropometric measurements, nutritional assessment, biochemical analysis, and clinical evaluation will be conducted to assess treatment outcomes. Statistical analysis will be performed to compare results between the two groups, employing SPSS version 19 with a significance level of P < .05., Conclusion: This randomized clinical trial aims to evaluate synbiotic supplementation effects on inflammatory markers and clinical outcomes in pediatric sepsis patients in the pediatric intensive care unit (PICU). Probiotics have shown promise in reducing proinflammatory cytokines like IL-6, TNF-α, and CRP, which are vital in the inflammatory response. Synbiotics can enhance gut integrity, preventing pathogen translocation and reducing inflammation. If our expectations regarding the effects of probiotics are correct, we can use them as a cost-effective supplement to improve the condition of pediatric sepsis in hospitals., Trial Registration: IRCT,IRCT20230523058266N1 Registered 30 October 2023, https://irct.behdasht.gov.ir/trial/71397 ., (© 2024. The Author(s).)

Objectives: To evaluate the effect of procalcitonin-guided management on the duration of antibiotic therapy in critically ill cancer patients with sepsis., Design: Randomized, controlled, single-blinded trial., Setting: A comprehensive multidisciplinary cancer hospital in Jordan., Patients: Adults with cancer treated in the ICU who were started on antibiotics for suspected infection, met the SEPSIS-3 criteria, and were expected to stay in the ICU greater than or equal to 48 hours., Interventions: Patients were randomized to the procalcitonin-guided or standard care (SC) arms. All patients had procalcitonin measured daily, up to 5 days or until ICU discharge or death. For the procalcitonin arm, a procalcitonin-guided algorithm was provided to guide antibiotic management, but clinicians were allowed to override the algorithm, if clinically indicated. In the SC arm, ICU clinicians were blinded to the procalcitonin levels., Measurements and Main Results: Primary outcome was time to antibiotic cessation. We also evaluated the number of antibiotic-free days at 28 days, hospital discharge, or death, whichever came first, and antibiotic defined daily doses (DDDs). We enrolled 77 patients in the procalcitonin arm and 76 in the SC arm. Mean age was 58 ± 14 (sd) years, 67% were males, 74% had solid tumors, and 13% were neutropenic. Median (interquartile range [IQR]) Sequential Organ Failure Assessment scores were 7 (6-10) and 7 (5-9) and procalcitonin concentrations (ng/mL) at baseline were 3.4 (0.8-16) and 3.4 (0.5-26), in the procalcitonin and SC arms, respectively. There was no difference in the median (IQR) time to antibiotic cessation in the procalcitonin and SC arms, 8 (4-11) and 8 (5-13), respectively (p = 0.463). Median (IQR) number of antibiotic-free days were 20 (17-24) and 20 (16-23), (p = 0.484) and total DDDs were 1541.4 and 2050.4 in the procalcitonin and SC arms, respectively., Conclusions: In critically ill cancer patients with sepsis, procalcitonin-guided management did not reduce the duration of antibiotic treatment., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background and Objectives : Diabetic foot sepsis (DFS) accounts for approximately 60% of hospital admissions in patients with diabetes mellitus (DM). Individuals with DM are at risk of severe COVID-19. This study investigated factors associated with major amputation and mortality in patients admitted with DFS during the COVID-19 pandemic. Materials and Methods : Demographic information, COVID-19 and HIV status, clinical findings, laboratory results, treatment and outcome from records of patients with diabetic foot sepsis, were collected and analysed. Supervised machine learning algorithms were used to compare their ability to predict mortality due to diabetic foot sepsis. Results : Overall, 114 records were found and 57.9% (66/114) were of male patients. The mean age of the patients was 55.7 (14) years and 47.4% (54/114) and 36% (41/114) tested positive for COVID-19 and HIV, respectively. The median c-reactive protein was 168 mg/dl, urea 7.8 mmol/L and creatinine 92 µmol/L. The mean potassium level was 4.8 ± 0.9 mmol, and glycosylated haemoglobin 11.2 ± 3%. The main outcomes included major amputation in 69.3% (79/114) and mortality of 37.7% (43/114) died. AI. The levels of potassium, urea, creatinine and HbA1c were significantly higher in the deceased. Conclusions : The COVID-19 pandemic led to an increase in the rate of major amputation and mortality in patients with DFS. The in-hospital mortality was higher in patients above 60 years of age who tested positive for COVID-19. The Random Forest algorithm of ML can be highly effective in predicting major amputation and death in patients with DFS.

The potential association between red blood cell distribution width (RDW) at admission and prognosis in patients with sepsis-induced cardiomyopathy(SIC) remains uncertain. The purpose of this study was to explore the prognostic value of RDW on mortality in patients with SIC. Data for this retrospective study were obtained from the MIMIC IV2.2 database. We used propensity score matching (PSM) and Cox proportional hazards regression analysis to evaluate the main risk factors associated with mortality in SIC patients. This analysis was utilized to develop a predictive nomogram. To assess the predictive accuracy and clinical usefulness of the model, we employed the concordance index (C-index) and decision curve analysis. To define the high- and low-RDW groups among patients with SIC, we determined the optimal cut-off value by maximizing the Youden index. According to the screening criteria, we identified a cohort of 1051 patients diagnosed with SIC. When comparing the high-RDW group to the low-RDW group, it was found that the high-RDW group exhibited longer Los&#95;ICU(4.5 days vs.3.8 days, respectively, P = 0.009) and higher mortality rates at 28 days (33.8% vs. 7.8%, respectively, P < 0.001). A nomogram model was created using matched patients which included various factors such as Age, RDW, LDH, CKMB, creatinine and the administration of β-blocker. The C-index predicting 28-day survival probability was 0.846. Decision curves analysis demonstrated that the inclusion of RDW in the model provided a greater net benefit compared to excluding RDW. The prognosis of patients with SIC can be predicted by the RDW value. The nomogram model provides a useful tool in identifying and managing SIC patients., (© 2024. The Author(s).)

Triglyceride-glucose (TyG) index has emerged as a novel biomarker for detecting insulin resistance (IR) and has been proven to be associated with various diseases. However, its correlation with the prognosis of severe sepsis remains unraveled. This retrospective cohort study utilized patient records from the Medical Information Mart for Intensive Care (MIMIC-IV, version 2.2) to examine the outcomes of patients with sepsis. The primary outcomes were hospital mortality and intensive care unit (ICU) mortality. The correlation between the TyG index and outcomes was evaluated through the Kaplan-Meier method, the Log-rank test, and univariate and multivariate Cox regression analyses. Additionally, restricted cubic spline (RCS) regression analysis was employed to delve into the nonlinear relationship between baseline TyG index and outcomes, with trend significance assessed through quartile levels. Subgroup analyses were conducted to evaluate the consistency of the TyG index's prognostic value across various influencing factors. The study included 1,742 patients with sepsis requiring intensive care. The in-hospital mortality rate was 19.75% (344/1,742), and the ICU mortality rate was 14.75% (257/1,742). Cox regression analysis revealed that, in comparison to the first quartile (Q1), patients in the fourth quartile (Q4) had a 63% higher risk of in-hospital mortality (HR 1.63 [95% CI 1.22 to 2.18], P < 0.01) and a 79% higher risk of ICU mortality (HR 1.79 [95% CI 1.28 to 2.51], P < 0.001). Model 3 showed that ICU mortality risks for Q4, Q3, and Q2 were 240%, 75%, and 33% higher, respectively (HR 3.40 [95% CI 2.24 to 5.16], P < 0.001; HR 1.75 [95% CI 1.16 to 2.63], P = 0.007; HR 1.33 [95% CI 1.20 to 1.53], P < 0.001). RCS regression analysis identified a nonlinear association between the TyG index and mortality (overall P < 0.001; P for nonlinearity < 0.001, with an inflection point at 8.9). Subgroup analysis showed that the effect size and direction were consistent across different subgroups, suggesting the stability of the results. This study demonstrates that a higher TyG index is significantly associated with increased in-hospital and ICU mortality risk in critically ill sepsis patients, with evidence of non-linear correlation. Therefore, the TyG index helps identify the mortality prognosis of sepsis patients in the ICU., (© 2024. The Author(s).)

Introduction: Sepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that ex vivo functional TNF expression as well as an immunologic endotype based on both IFNγ and TNF expression could be used to model clinical outcomes in sepsis patients., Methods: This prospective, observational study of patient samples collected from the SPIES consortium included patients at five health systems enrolled over 17 months, with 46 healthy control patients, 68 ICU patients without sepsis, and 107 ICU patients with sepsis. Whole blood was collected on day 1, 4, and 7 of ICU admission. Outcomes included in-hospital and 180-day mortality and non-favorable discharge disposition defined by skilled nursing facility, long-term acute care facility, or hospice. Whole blood ELISpot assays were conducted to quantify TNF expression [stimulated by lipopolysaccharide (LPS)] and IFNγ expression (stimulated by anti-CD3/CD28 mAb), which were then used for assignment to one of four subgroups including an 'immunocompetent', 'immunosuppressed endotype', and two 'mixed' endotypes., Results: Whole blood TNF spot-forming units were significantly increased in septic and CINS patients on days 4 and 7 compared to healthy subjects. In contrast, TNF expression per cell on days 1, 4, and 7 was significantly lower in both septic and critically ill non-septic (CINS) patients compared to healthy subjects. Early increases in total TNF expression were associated with favorable discharge disposition and lower in-hospital mortality. 'Immunocompetent' endotype patients on day 1 had a higher proportion of favorable to non-favorable discharges compared to the 'immunosuppressed' endotype. Similarly, 'immunocompetent' endotype patients on day 4 had a higher in-hospital survival compared to the 'immunosuppressed' endotype patients. Finally, among septic patients, decreased total TNF and IFNγ expression were associated with 180-day mortality., Conclusions: Increased ex vivo whole blood TNF expression is associated with improved clinical outcomes. Further, the early 'immunocompetent' endotype is associated with favorable discharge and improved in-hospital and 180-day survival. The ability to functionally stratify septic patients based on blood cell function ex vivo may allow for identification of future immune modulating therapies., Competing Interests: MM is a member of Immune Functional Diagnostics, LLC and receives no direct financial compensation. Immune Functional Diagnostics, LLC is developing predictive metrics in critical illness and this technology is evaluated in this research. KR is a member of Immune Functional Diagnostics, LLC and receives no direct financial compensation. Immune Functional Diagnostics, LLC is developing predictive metrics in critical illness and this technology is evaluated in this research. SB and the University of Florida may receive royalty income based on a technology developed by SB and others and licensed by Washington University in St. Louis to IFDx LLC. That technology is evaluated in this research. LM and the University of Florida may receive royalty income based on a technology developed by LM and others and licensed by Washington University in St. Louis to IFDx LLC. That technology is evaluated in this research. RH and Washington University in St. Louis may receive royalty income based on a technology developed by RH and others and licensed by Washington University in St. Louis to IFDx LLC. That technology is evaluated in this research. He is also supported by R35 GM-126928, awarded by the National Institute of General Medical Sciences. CC is supported by NIH grant R01GM139046. CC and the University of Cincinnati may receive royalty income based on a technology developed by CC and others and licensed by Washington University in St. Louis to IFDx LLC. That technology is evaluated in this research., (Copyright © 2024 Price, Becker, Barrios, Mazer, McGonagill, Bergmann, Goodman, Gould, Rao, Polcz, Kucaba, Walton, Miles, Xu, Liang, Loftus, Efron, Remy, Brakenridge, Badovinac, Griffith, Moldawer, Hotchkiss and Caldwell.)

Sepsis and septic shock remain global healthcare problems associated with high mortality rates despite best therapy efforts. Circulating biomarkers may identify those patients at risk for poor outcomes, however, current biomarkers, most prominently lactate, are non-specific and have an inconsistent impact on prognosis and/or disease management. Activation of the renin-angiotensin- system (RAS) is an early event in sepsis patients and elevated levels of circulating renin are more predictive of worse outcomes than lactate. The precursor protein Angiotensinogen is another key component of the circulating RAS; it is the only known substrate for renin and the ultimate source of the vasopressor Angiotensin II (Ang II). We postulate that lower Angiotensinogen concentrations may reflect a dysfunctional RAS characterized by high renin concentrations but attenuated Ang II generation, which is disproportionate to the high renin response and may compromise adequate support of blood pressure and tissue perfusion in septic patients. The current study compared the association between serum Angiotensinogen with mortality to that of lactate and renin in the VICTAS cohort of sepsis patients at baseline (day 0) by receiver operating characteristic (ROC) and Kaplan-Meier curve analyses. Serum concentration of Angiotensinogen was more strongly associated with 30-day mortality than either the serum concentrations of renin or lactate in sepsis patients. Moreover, the clinical assessment of Angiotensinogen may have distinct advantages over the typical measures of renin. The assessment of intact Angiotensinogen may potentially facilitate more precise therapeutic approaches (including exogenous angiotensin II) to restore a dysfunctional RAS and improve patient outcomes. Additional prospective validation studies are clearly required for this biomarker in the future., (© 2024. The Author(s).)

This data descriptor presents a curated dataset for pathogen detection and identification (Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans) directly from whole-blood samples. The dataset was created using differential cell lysis combined with rapid extraction, digestion, and mass spectrometry-based proteomics. Our method offers a rapid diagnostic alternative to traditional culture, enabling timely disease management, such as sepsis. Highlighting our dataset's uniqueness, it features a three-tier structure: Spectral Libraries of Pathogens for identifying peptide peaks for putative biomarkers; Spiked pathogen in blood MS data for biomarker panel optimization through varied concentration samples; and Parallel Reaction Monitoring (PRM) data from sepsis patients for validating our biomarker panel, achieving 83.3% sensitivity within seven hours without microbial enrichment culture. This dataset serves as a comprehensive reference for bioinformatic tool development and biomarker panel proposals, advancing microbial detection, antimicrobial resistance, and epidemiological studies., (© 2024. The Author(s).)

Background: Early recognition of sepsis by the EMS (Emergency Medical Services), along with communicating this concern to the emergency department, could improve patient prognosis and outcome. Knowledge is limited about the performance of sepsis identification screening tools in the EMS setting. Research is also limited on the effectiveness of prehospital use of blood tests for sepsis identification. Integrating blood analyses with screening tools could improve sepsis identification, leading to prompt interventions and improved patient outcomes., Aim: The aim of the present study is firstly to evaluate the performance of various screening tools for sepsis identification in the EMS setting and secondly to assess the potential improvement in accuracy by incorporating blood analyses., Methods: This is a retrospective observational cohort study. The data were collected from prehospital and hospital medical records in Region Halland. Data on demographics, vital signs, blood tests, treatment, and outcomes were collected from patients suspected by EMS personnel of having infection. The data were analysed using Student's t-test. Sensitivity, specificity, positive predictive value, negative predictive value and odds ratio were used to indicate accuracy and predictive value., Results: In total, 5,405 EMS missions concerning 3,225 unique patients were included. The incidence of sepsis was 9.8%. None of the eleven tools included had both high sensitivity and specificity for sepsis identification. White blood cell (WBC) count was the blood analysis with the highest sensitivity but the lowest specificity for identifying sepsis. Adding WBC, C-reactive protein (CRP) or lactate to the National Early Warning Score (NEWS) increased the specificity to > 80% but substantially lowered the sensitivity., Conclusions: Identifying sepsis in EMS settings remains challenging, with existing screening tools offering limited accuracy. CRP, WBC, and lactate blood tests add minimal predictive value in distinguishing sepsis or determining non-conveyance eligibility., (© 2024. The Author(s).)

Damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) are key triggers of inflammation in sepsis. However, they have rarely been studied simultaneously. Thus, in the present study of patients with bacteraemic infection, we aimed to study how DAMP dynamics are linked to disease severity and outcome and to compare diagnostic and prognostic properties of a DAMP and a previously analysed PAMP (16S rDNA). In a prospective study of adult patients hospitalized with culture-proven community-onset bacteraemic infection, caused by Streptococcus pneumonia (n = 30), Staphylococcus aureus (n = 27), or Escherichia coli (n = 26), dynamics of a PAMP, i.e. 16S rDNA, have previously been presented. For the present study, blood samples obtained on hospital days 1-2 (when blood culture was positive), 3-4, 7 ± 1, 14 ± 2, and 28 ± 4 were analysed for four different DAMPs, i.e., nuclear DNA (nDNA), mitochondrial DNA (mtDNA), heat shock protein 90 alpha (HSP90α), and extracellular high mobility group box 1 (HMGB1). Sepsis was defined according to the Sepsis-3 criteria. The study outcomes were sepsis at admission and negative outcome, defined as intensive care unit (ICU) admission and/or death within 60 days. Of 83 study patients, sepsis was noted in 41 patients (49%) and a negative outcome was noted in 17 patients (20%). nDNA had areas under the receiver operating characteristic (ROC) curves of 0.78 for sepsis and 0.76 for negative outcome, which were higher than those of the other DAMPs and additional biomarkers (CRP, IL-6, IL-8, and IL-10). The nDNA and positive 16S rDNA results on day 1-2 were correlated with each other (r = 0.68, p < 0.001). Multivariate analyses showed that high day 1-2 concentrations of both nDNA and 16S rDNA were independently associated with sepsis. In addition, high day 1-2 concentration of nDNA was independently associated with negative outcomes. While 16S rDNA dissipated from the circulation within days, nDNA concentrations remained elevated throughout the follow-up period in patients with negative outcome. In conclusion, nDNA outperformed the other DAMPs regarding sepsis detection and outcome prediction. Both nDNA (a DAMP) and 16S rDNA (a PAMP) were independently linked to sepsis; nDNA was also associated with negative outcomes and persisted elevated in such cases. This highlights nDNA as an interesting marker within sepsis pathogenesis and as a promising clinical biomarker, warranting further studies., (© 2024. The Author(s).)

To explore the application value of SAA (serum amyloid A), CRP (C reactive protein), PCT (procalcitonin), WBC (white blood cell) and N% (neutrophil %) in the diagnosis of neonatal septicemia. This study was a retrospective study. 173 children with clinically diagnosed septicemia and 66 children with definitely diagnosed septicemia admitted to the Department of Neonatology, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China,from January 2022 to January 2024 were selected as the case group, and 148 children with neonatal jaundice who were hospitalized during the same period were selected as the control group. Fasting venous blood was collected within 24 hours after the children's admission to detect the levels of serum WBC, N%, SAA, CRP and PCT. One-way analysis of variance and Kruskal-Wallis H test were used to compare the general data and inflammatory index levels of the three groups of children. The correlation analysis between SAA and other inflammatory indicators was conducted using Spearman correlation analysis. The receiver operating characteristic (ROC) curve was used to determine the diagnostic efficacy of different inflammatory indicators for patients with definitely diagnosed septicemia and those with clinically diagnosed septicemia, and for those with clinically diagnosed septicemia and those without infection. The results showed that the levels of WBC [(16.88±5.64)×10 9 /L], N% [70.00 (63.00, 75.00)], PCT [2.22 (1.20, 5.55) mg/L], CRP [3.00 (0.50, 10.30) mg/L], SAA [19.70 (10.82, 49.90) mg/L] in the clinically diagnosed septicemia group and WBC [(16.10±7.48)×10 9 /L], N% [73.50 (61.50, 80.93)], PCT [5.35 (0.69, 20.07) mg/L], CRP [15.52 (4.98, 30.50) mg/L], SAA [43.95 (14.00, 175.98) mg/L] in the definitely diagnosed septicemia group were all higher than those in the control group (11.17±3.38)×10 9 /L, 49.81 (36.93, 62.75), 0.20 (0.07, 0.99) mg/L, 0.54 (0.20, 1.40) mg/L, 5.15 (3.60, 8.68) mg/L, and the differences were all statistically significant (all P< 0.05). Spearman correlation analysis showed that the level of SAA was positively correlated with WBC, N%, PCT and CRP ( r s =0.453, 0.540, 0.343, 0.550, all P <0.05). ROC curve analysis showed that the area under ROC curve(AUC) of SAA for the definitely diagnosed septicemia group and the clinically diagnosed septicemia group was higher than that of other inflammatory indicators, among them, the AUC of SAA for diagnosing the definitely diagnosed neonatal septicemia group was 0.933 (95% CI : 0.809-1.000, P <0.05), with a sensitivity of 92.90% and a specificity of 99.30%. The AUC of SAA for diagnosing the clinically diagnosed septicemia group was 0.861 (95% CI : 0.818-0.904, P <0.05), with a sensitivity of 83.20% and a specificity of 81.80%. In conclusion, compared with CRP, PCT, WBC and N%, SAA has higher sensitivity and specificity for distinguishing neonatal septicemia (including definitely diagnosed septicemia and clinically diagnosed septicemia), and has certain auxiliary diagnostic value for neonatal septicemia.

Background: Sepsis is defined as a dysfunctional host response to infection. The diverse clinical presentations of sepsis pose diagnostic challenges and there is a demand for enhanced diagnostic markers for sepsis as well as an understanding of the underlying pathological mechanisms involved in sepsis. From this perspective, metabolomics has emerged as a potentially valuable tool for aiding in the early identification of sepsis that could highlight key metabolic pathways and underlying pathological mechanisms., Objective: The aim of this investigation is to explore the early metabolomic and lipidomic profiles in a prospective cohort where plasma samples (n = 138) were obtained during ambulance transport among patients with infection according to clinical judgement who subsequently developed sepsis, patients who developed non-septic infection, and symptomatic controls without an infection., Methods: Multiplatform metabolomics and lipidomics were performed using UHPLC-MS/MS and UHPLC-QTOFMS. Uni- and multivariable analysis were used to identify metabolite profiles in sepsis vs symptomatic control and sepsis vs non-septic infection., Results: Univariable analysis disclosed that out of the 457 annotated metabolites measured across three different platforms, 23 polar, 27 semipolar metabolites and 133 molecular lipids exhibited significant differences between patients who developed sepsis and symptomatic controls following correction for multiple testing. Furthermore, 84 metabolites remained significantly different between sepsis and symptomatic controls following adjustment for age, sex, and Charlson comorbidity score. Notably, no significant differences were identified in metabolites levels when comparing patients with sepsis and non-septic infection in univariable and multivariable analyses., Conclusion: Overall, we found that the metabolome, including the lipidome, was decreased in patients experiencing infection and sepsis, with no significant differences between the two conditions. This finding indicates that the observed metabolic profiles are shared between both infection and sepsis, rather than being exclusive to sepsis alone., (© 2024. The Author(s).)

The discovery of Lactylation may pave the way for novel approaches to investigating sepsis. This study focused on the prognostic and diagnostic significance of lactylated genes in sepsis. RNA sequencing was performed on blood samples from 20 sepsis patients and 10 healthy individuals at Southwest Medical University in Luzhou, Sichuan, China. Genes associated with sepsis were identified through analysis of RNA sequencing data. Afterward, the genes that were expressed differently were compared with the lactylation genes, resulting in the identification of 55 lactylation genes linked to sepsis. The overlapping genes underwent analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-Protein Network Interactions were used to screen for the core genes. The datasets GSE65682, GSE69528, GSE54514, GSE63042, and GSE95233 were obtained from the GEO database to validate core genes. Survival analysis evaluated the predictive significance of central genes in sepsis, while Receiver Operating Characteristic (ROC) Curve analysis was employed to establish the diagnostic value of genes. Additionally, a meta-analysis was conducted to confirm the precision of RNA-seq data. We obtained five peripheral blood samples, including two from healthy individuals, one from a patient with systemic inflammatory response syndrome (SIRS), and two from patients with sepsis. These samples were used to identify the specific location of core genes using 10×single-cell sequencing. High-throughput sequencing and bioinformatics techniques identified two lactylation-related genes (S100A11 and CCNA2) associated with sepsis. Survival analysis indicated that septic patients with reduced levels of S100A11 had a decreased 28-day survival rate compared to those with elevated levels. Conversely, individuals exhibiting decreased CCNA2 levels demonstrated a greater likelihood of surviving for 28 days than those in the high expression category, indicating a favorable association with survival rates among sepsis patients (P < 0.05). Both genes showed high sensitivity and specificity based on the ROC curve, with AUC values of 0.961 for S100A11 and 0.890 for CCNA2. The meta-analysis revealed that S100A11 exhibited high levels of expression in the sepsis survivors, whereas it displayed low levels of expression in the non-survivors; on the other hand, CCNA2 demonstrated low expression in the sepsis survivors and high expression in the non-survivors (P < 0.05). Single-cell RNA sequencing ultimately showed that monocyte macrophages, T cells, and B cells exhibited high expression levels of the crucial genes associated with sepsis-induced lactylation. In conclusion, the lactylation genes S100A11 and CCNA2 are strongly linked to sepsis and could be valuable markers for diagnosing, predicting outcomes, and providing guidance for sepsis., (© 2024. The Author(s).)

Intracerebral hemorrhage (ICH) could trigger inflammatory responses. However, the specific role of inflammatory proteins in the pathological mechanism, complications, and prognosis of ICH remains unclear. In this study, we investigated the expression of 92 plasma inflammation-related proteins in patients with ICH ( n = 55) and healthy controls ( n = 20) using an Olink inflammation panel and discussed the relation to the severity of stroke, clinical complications, 30-day mortality, and 90-day outcomes. Our result showed that six proteins were upregulated in ICH patients compared with healthy controls, while seventy-four proteins were downregulated. In patients with ICH, seven proteins were increased in the severe stroke group compared with the moderate stroke group. In terms of complications, two proteins were downregulated in patients with pneumonia, while nine proteins were upregulated in patients with sepsis. Compared with the survival group, three proteins were upregulated, and one protein was downregulated in the death group. Compared with the good outcome group, eight proteins were upregulated, and four proteins were downregulated in the poor outcome group. In summary, an in-depth exploration of the differential inflammatory factors in the early stages of ICH could deepen our understanding of the pathogenesis of ICH, predict patient prognosis, and explore new treatment strategies.

Objective To analyze the risk factors of septic cardiomyopathy (SC),and to construct and evaluate the risk prediction model of SC. Methods The clinical data of patients with sepsis were extracted from MIMIC-Ⅳ database and randomized into a training set and a validation set at a ratio of 7 to 3.According to the presence or absence of SC,the patients were assigned into SC and non-SC groups.The independent risk factors of SC were determined by univariate and multivariate Logistic regression analysis,and a risk prediction model and a nomogram were established.The area under the receiver operating characteristic curve (AUC),calibration curve,and decision curve analysis (DCA) were employed to evaluate the distinguishing degree,calibration,and clinical applicability of the model,respectively. Results A total of 2628 sepsis patients were enrolled in this study,including 1865 patients in the training set and 763 patients in the validation set.There was no significant difference in the incidence of SC between the training set and the validation set (58.98% vs. 62.25%, P =0.120).Except chronic obstructive pulmonary disease ( P =0.015) and length of stay in intensive care unit ( P =0.016),there was no significant difference in other clinical indicators between the two groups (all P >0.05).Logistic regression analysis showed that coronary heart disease ( P =0.028),heart failure ( P <0.001),increased neutrophil count ( P =0.001),decreased lymphocyte count ( P =0.036),increased creatine kinase isoenzyme ( P <0.001),and increased blood urea nitrogen ( P =0.042) were independent risk factors for SC.The AUC of the nomogram prediction model in the training set and validation set was 0.759 (95% CI =0.732-0.785) and 0.765 (95% CI =0.723-0.807),respectively.The established model showcased good fitting degrees in both data sets (training set: P =0.075;validation set: P =0.067).The DCA results showed that the nomogram prediction model had good clinical applicability. Conclusion The nomogram prediction model based on basic diseases and clinical biochemical indicators can effectively predict the risk of SC occurrence.

Globally, sepsis is the primary cause of death for children. While research conducted on adults has a significant impact on the diagnosis and treatment of sepsis in newborns and young children, there are significant factors that are pertinent to pediatrics as well. This prospective case-control study was conducted during the period from August 2020 to October 2022 after approval by the institutional ethical committee. The study included 48 critically ill children admitted at the Pediatric intensive care unit and 30 apparently healthy children as a control group. Laboratory investigations including complete blood picture, C-reactive protein (CRP), blood culture and sensitivity and plasma level of cluster of differentiation 64 (CD64) and myeloperoxidase (MPO) were investigated for all participants. A daily follow up for the signs of systemic inflammatory response syndrome (SIRS) or sepsis was done, and the patients were divided into SIRS and non-SIRS subgroups then patients were divided into two groups according to the presence of severe sepsis. A follow up CD64 and MPO sample were withdrawn from them to assess their prognostic value. SIRS was reported in 39.58 % of patients while severe sepsis was reported in 20.8%. CD64 and MPO were significantly higher in cases than controls (p= 0.003, p < 0.001, respectively) and, in patients with SIRs and severe sepsis CD64 was 1559.00± 367.09 pg/ml and 1547.9 4± 436.14 pg/ml, respectively. Also, MPO was significantly higher in patients with SIRS (113.58± 25.19 mU/ml) and severe sepsis (111.70± 26.50 mU/ml). CD64 and MPO significantly increased after development of sepsis in admitted patients. ROC was significantly higher for CD64 and MPO at admission than that for CRP at admission (p=0.123, p=0.014, respectively). In conclusion, plasma level of CD64 and MPO in peripheral blood can be considered an early sensitive marker for the detection and follow up of pediatric sepsis., (Copyright© by the Egyptian Association of Immunologists.)

Purpose: The triglyceride-glucose (TyG) index is a surrogate biomarker of insulin resistance which has been widely used in intensive care unit (ICU) to predict prognosis. However, its role in critically ill acute exacerbation of COPD (AECOPD) patients remains largely unknown., Material and Methods: A total of 645 AECOPD patients were induced in this retrospective cohort study, which extracted data from the eICU Collaborative Research Database (eICU-CRD). The TyG index was calculated as Ln (fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2). The primary endpoint includes in-hospital mortality and ICU mortality. The secondary endpoint was sepsis, acute kidney injury (AKI), and acute respiratory failure (ARF)., Results: Multivariable Cox regression analysis revealed that the TyG index was independently associated with an increased risk of in-hospital mortality (hazard ratio, HR: 1.45, 95% CI: 1.04-2.01, P = 0.028) and ICU mortality (HR: 2.13, 95% CI: 1.28-3.54, P = 0.004). Moreover, the TyG index was independently associated with an increased risk of sepsis (odds ratio, OR: 1.54, 95% CI: 1.24-1.93, P < 0.001), AKI (OR: 1.57, 95% CI: 1.26-2.02, P < 0.001) and ARF (OR: 1.50, 95% CI: 1.20-1.87, P < 0.001). Kaplan-Meier survival analysis revealed that higher TyG indexes were also related to increased in-hospital mortality and ICU mortality. In addition, the restricted cubic splines regression model demonstrated that the in-hospital mortality and ICU mortality increased linearly with increasing TyG index (P for non-linearity = 0.897, P for non-linearity = 0.897, respectively)., Conclusion: Elevated TyG index was independently associated with an increased risk of poor clinical outcomes in critically ill AECOPD patients. A prospective study to define TyG as a biomarker for prognosis prediction in critically ill AECOPD patients is warranted., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 Wang et al.)

This study addresses the challenge of predicting mortality in sepsis among burn patients. Given the heterogeneity of sepsis, especially in the context of burn injuries, this study aims to identify reliable biomarkers for mortality prediction. The study is a retrospective review, focusing on the evaluation of various biomarkers and their changes over time in a burn patient cohort. Conducted in the Burn Intensive Care Unit of Hangang Sacred Heart Hospital, the study involved a retrospective review of 1,659 adult burn patients from January 2010 to December 2022. Key biomarkers analyzed include lactate levels, pH, platelets, procalcitonin, and others. Advanced clustering methodologies, such as dynamic time warping and hierarchical clustering, were utilized to classify patients into distinct groups based on their biomarker profiles and clinical outcomes. The study identified four patient clusters with unique lactate level trajectories. Significant findings include the identification of procalcitonin, pH, and platelets as key predictors of mortality, with varying degrees of efficacy across different clusters. For instance, in the "Persistent Rise" cluster, pH and platelet count showed Area Under the Curve (AUC) values of 0.756 and 0.753, respectively, indicating their strong predictive power. The study concludes that a combination of biomarkers, especially lactate dynamics, can effectively predict mortality in burn-induced sepsis. The results advocate for a more personalized approach in managing sepsis in burn patients, considering the specific biomarker trajectories. These findings are crucial for enhancing treatment strategies and improving patient outcomes in burn care., (© 2024. The Author(s).)

Background: The relationship between the dynamic changes in insulin resistance (IR) and the prognosis of septic patients remains unclear. This study aims to investigate the correlation between the clinical subphenotype of IR represented by the triglyceride-glucose (TyG) index trajectory and the mortality rate among patients with sepsis., Methods: In this retrospective cohort study, we utilized data from septic patients within the Medical Information Mart for Intensive Care (MIMIC)-IV database version 2.0 to construct trajectories of the TyG index over 72 h. Subsequently, we computed the similarity among various TyG index trajectories with the dynamic time warping (DTW) algorithm and utilized the hierarchical clustering (HC) algorithm to demarcate distinct cluster and identified subphenotypes according to the trajectory trend. Subsequently, we assessed the mortality risk between different subphenotypes using analyses such as survival analysis and validated the robustness of the results through propensity score matching (PSM) and various models., Results: A total of 2350 patients were included in the study. Two trajectory trends: TyG index decreasing (n = 926) and TyG index increasing (n = 1424) were identified, which indicated corresponding to the clinical subphenotype of increased and alleviative IR respectively. The 28-day and in-hospital mortality for the increased IR group was 28.51% and 25.49% respectively. In comparison, patients in the alleviative IR group with a 28-day mortality of 23.54% and an in-hospital mortality of 21.60%. These subphenotypes exhibited distinct prognosis, time dependent Cox model showed the increased IR group with a higher 28-day mortality [hazard ratio (HR): 1.07, 95% confidence interval (CI): 1.02-1.12, P = 0.01] and in-hospital mortality [HR: 1.05, 95% CI: 1.00-1.11, P = 0.045] compared to the alleviative IR group. Sensitivity analyses with various models further validated the robustness of our findings., Conclusion: Dynamic increase in the TyG index trajectory is associated with elevated mortality risk among patients with sepsis, which suggests that dynamic increased IR exacerbates the risk of poor outcomes in patients., (© 2024. The Author(s).)

Studies have pointed to a decisive role of autoantibodies in the context of sepsis and severe Coronavirus disease 2019 (COVID-19), which itself often fulfills the criteria for sepsis, including dysregulated immune responses and organ dysfunction. To directly compare and further analyze the autoantibody profiles of sepsis patients with and without COVID-19, the luciferase immunoprecipitation systems (LIPS) assay was used to measure the levels of autoantibodies against a variety of clinically relevant cytokines, lung-associated proteins, other autoantigens, and antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, cytokine titers were measured with the LEGENDplex™ Human Antivirus Response Panel. We observed significantly increased levels of autoantibodies in 59% of the COVID-19-Sepsis group compared to 48% of the Sepsis group. Significant differences were identified between the groups for the levels of autoantibodies against gATPase. The cytokine levels of interferon (IFN)-λ1 and IP-10 were higher in the COVID-19-Sepsis group compared to the Sepsis group. Additional correlations between autoantibodies, cytokines and 30-day survival could be demonstrated, suggesting varied underlying pathological mechanisms. Elevated levels of cytokines and autoantibodies may serve as prognostic indicators for the survival probability of sepsis patients, highlighting the intricate relationship between immune responses and patient outcomes in the context of both sepsis and COVID-19., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: The clinical value of procalcitonin (PCT) in infection diagnosis and antibiotic stewardship is still unclear. This study aimed to investigate the association between serum PCT and different clinical conditions as well as other infectious/inflammatory parameters in different septic patients in order to elucidate the value of PCT detection in infection management., Methods: Chemiluminescence immunoassay was used for serum PCT analysis. Hematology analysis was used for complete blood cell count. Digital automated cell morphology analysis was used for blood cell morphology examination. Blood, urine, and stool cultures were performed according to routine clinical laboratory standard operating procedures. C-reactive protein (CRP) was analyzed by immunoturbidimetry. Erythrocyte sedimentation rate test was performed using natural sedimentation methods., Results: Outpatients, ICU patients, and patients under 2 years of age with respiratory infections had higher serum PCT levels. Septic patients had the highest-serum PCT levels and other infection indexes. PCT levels in the blood, urine, and stool culture-positive patients were significantly higher than in culture-negative patients. The neutrophil granulation and reactive lymphocytes were observed together with the PCT-level increments in different septic patients, and these alterations were lessened after treatment. There was no significant change in monocyte morphology between pre- and posttreatment septic patients., Conclusions: Serum PCT is associated with neutrophil cytotoxicity and lymphocyte morphology changes in sepsis; thus, the combination of neutrophil and lymphocyte digital cell morphology evaluations with PCT detection may be a useful examination for guiding the clinical management of sepsis., (© 2024 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: The coexistence of sepsis and hematological malignancies increases patient vulnerability, revealing the need for precise prognostic markers. This study explores the prognostic significance of lactate levels and clearance in septic patients with hematological malignancies., Materials and Methods: A retrospective cohort study from January 2016 to December 2019 in a tertiary hematological intensive care unit (ICU) included 167 adults with hematological malignancies and sepsis. The relationship between lactate levels, hyperlactatemia, lactate clearance, and ICU outcomes was investigated. ICU survivors and non-survivors were compared to identify the factors affecting ICU mortality., Results: Patients were primarily with lymphoma and acute leukemia (66%) and had frequent hyperlactatemia (64%) on ICU admission. ICU non-survivors demonstrated higher lactate levels and hyperlactatemia frequency at various time points (0, 6, and 12 h) than survivors. Lactate clearance and liver function tests did not differ significantly between the two groups. Invasive mechanical ventilation [OR (95% confidence interval-CI): 20.4 (2.4-79.8), p < 0.01], requirement of vasopressors [OR (95% CI): 5.6 (1.3-24.5), p < 0.01], lactate level at the 6th hour [OR (95% CI): 1.51 (1.1-2.07), p = 0.01], and APACHE II score (OR (95% CI): 1.16 (1.01-1.34), p = 0.05) were independent risk factors for ICU mortality. The Area Under the Curve for APACHE II score and lactate level at the 6th hour were 0.774 (95% CI: 0.682-0.866) and 0.703 (95% CI: 0.602-0.804), respectively., Conclusion: While elevated lactate levels correlate with mortality rate and lactate level at the 6th hour is an independent risk factor for mortality, the absence of a significant difference in lactate clearance challenges traditional assumptions. These results question the commonly accepted perspective regarding lactate dynamics in sepsis among individuals with hematological malignancies., Oral Presentation: İnci K, et al. "Hyperlactatemia, lactate clearance and outcome in critically ill patients with hematological malignancies," 22nd ınternational intensive care symposium, 2019., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Sepsis is a recognized global health challenge that places a considerable disease burden on countries. Although there has been some progress in the study of sepsis, the mortality rate of sepsis remains high. The relationship between serum osmolality and the prognosis of patients with sepsis is unclear., Method: Patients with sepsis who met the criteria in the Medical Information Mart for Intensive Care IV database were included in the study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined using multivariable Cox regression. The relationship between serum osmolality and the 28-day mortality risk in patients with sepsis was investigated using curve fitting, and inflection points were calculated., Results: A total of 13,219 patients with sepsis were enrolled in the study; the mean age was 65.1 years, 56.9 % were male, and the 28-day mortality rate was 18.8 %. After adjusting for covariates, the risk of 28-day mortality was elevated by 99% (HR 1.99, 95%CI 1.74-2.28) in the highest quintile of serum osmolality (Q5 >303.21) and by 59% (HR 1.59, 95%CI 1.39-1.83) in the lowest quintile (Q1 ≤285.80), as compared to the reference quintile (Q3 291.38-296.29). The results of the curve fitting showed a U-shaped relationship between serum osmolality and the risk of 28-day mortality, with an inflection point of 286.9 mmol/L., Conclusion: There is a U-shaped relationship between serum osmolality and the 28-day mortality risk in patients with sepsis. Higher or lower serum osmolality is associated with an increased risk of mortality in patients with sepsis. Patients with sepsis have a lower risk of mortality when their osmolality is 285.80-296.29 mmol/L., (© 2024. The Author(s).)

This study aimed to investigate whether changes in presepsin, procalcitonin, high-sensitivity C-reactive protein, and interleukin 6 levels predict mortality in septic patients in the intensive care unit. This study enrolled septic patients between November 2020 and December 2021. Levels of presepsin, procalcitonin, high-sensitivity C-reactive protein, and interleukin 6 were measured on the first (PSEP&#95;0, PCT&#95;0, hsCRP&#95;0, IL-6&#95;0) and third days (PSEP&#95;3, PCT&#95;3, hsCRP&#95;3, IL-6&#95;3). Follow-up was performed on days 3, 7, 14, 21, and 28 after enrollment. The outcome was all-cause death. The study included 119 participants, and the mortality was 18.5%. In univariable Cox proportional hazards regression analysis, ΔPSEP (= PSEP&#95;3 - PSEP&#95;0) > 211.49 pg/mL (hazard ratio, 2.70; 95% confidence interval, 1.17-6.22), ΔPCT (= PCT&#95;3 - PCT&#95;0) > -0.13 ng/mL (hazard ratio, 7.31; 95% confidence interval, 2.68-19.80), ΔhsCRP (= hsCRP&#95;3 - hsCRP&#95;0) > -19.29 mg/L (hazard ratio, 6.89; 95% confidence interval, 1.61-29.40), and ΔIL-6 (= IL-6&#95;3 - IL-6&#95;0) > 1.00 pg/mL (hazard ratio, 3.13; 95% confidence interval, 1.35-7.24) indicated an increased risk of mortality. The composite concordance index for alterations in all 4 distinct biomarkers was highest (concordance index, 0.83; 95% confidence interval, 0.76-0.91), suggesting the optimal performance of this panel in mortality prediction. In decision curve analysis, compared with the Acute Physiology and Chronic Health Evaluation II and Sequential (sepsis-related) Organ Failure Assessment scores, the combination of the 4 biomarkers had a larger net benefit. Interestingly, interleukin 6 was predominantly produced by monocytes upon lipopolysaccharide stimulation in peripheral blood mononuclear cells. ΔPSEP, ΔPCT, ΔhsCRP, and ΔIL-6 are reliable biomarkers for predicting mortality in septic patients in the intensive care unit, and their combination has the best performance., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Abstract: Background: Pediatric sepsis is a common and complex syndrome characterized by a dysregulated immune response to infection. Aberrations in the renin-angiotensin system (RAS) are factors in several infections of adults. However, the precise impact of RAS dysregulation in pediatric sepsis remains unclear. Methods: Serum samples were collected from a derivation cohort (58 patients with sepsis, 14 critically ill control subjects, and 37 healthy controls) and validation cohort (50 patients with sepsis, 37 critically ill control subjects, and 46 healthy controls). Serum RAS levels on day of pediatric intensive care unit admission were determined and compared with survival status and organ dysfunction. Results: In the derivation cohort, the serum renin concentration was significantly higher in patients with sepsis (3,678 ± 4,746) than that in healthy controls (635.6 ± 199.8) ( P < 0.0001). Meanwhile, the serum angiotensin (1-7) was significantly lower in patients with sepsis (89.7 ± 59.7) compared to that in healthy controls (131.4 ± 66.4) ( P < 0.01). These trends were confirmed in a validation cohort. Nonsurvivors had higher levels of renin (8,207 ± 7,903) compared to survivors (2,433 ± 3,193) ( P = 0.0001) and lower levels of angiotensin (1-7) (60.9 ± 51.1) compared to survivors (104.0 ± 85.1) ( P < 0.05). A combination of renin, angiotensin (1-7) and procalcitonin achieved a model for diagnosis with an area under the receiver operating curve of 0.87 (95% CI: 0.81-0.92). Conclusion: Circulating renin and angiotensin (1-7) have predictive value in pediatric sepsis., Competing Interests: The authors report no conflicts of interest. The authors have no other conflicts of interest to declare., (Copyright © 2024 by the Shock Society.)

Abstract: Purpose : This study aimed to investigate the presence of schistocytes in patients with sepsis and its association with mortality and organ failure. Methods : We conducted a retrospective observational study at Shiga University of Medical Science Hospital, Japan, from January 2015 to April 2021. This study included patients diagnosed with sepsis or septic shock. Schistocytes were identified through daily hematological examinations. Moreover, data on mortality rates and organ failure based on Sequential Organ Failure Assessment scores were systematically collected and analyzed. Results : Schistocytes were detected in 41 of the 330 patients with sepsis. The presence of schistocytes was associated with significantly high 90-day and 1-year mortality rates (48.7% and 68.2%, respectively; P < 0.001). Patients with schistocytes exhibited higher Sequential Organ Failure Assessment scores, particularly in the coagulation and renal components, indicating more severe organ failure than that observed in patients without schistocytes. These findings persisted even after adjusting for confounding factors, such as age, sex, and baseline comorbidities. Additionally, we observed that patients with schistocytes required frequent red blood cells, further highlighting the severity of their conditions. Conclusion : Schistocytes are significantly associated with increased long-term mortality and organ failure in patients with sepsis. Their detection may provide crucial insights into disease severity, guide targeted therapeutic strategies, and potentially improve the long-term outcomes of sepsis management., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Background: The adverse effects of sepsis-associated acute kidney injury (SA-AKI) highlight the need for new biomarkers. Signal Peptide-Complement C1r/C1s, Uegf, Bmp1-Epidermal Growth Factor-like Domain-Containing Protein 2 (SCUBE2), important for angiogenesis and endothelial integrity, has been linked to increased mortality in models of lipopolysaccharide-induced lung injury. This research aimed to assess the utility of plasma SCUBE2 levels as a prognostic indicator for SA-AKI in intensive care unit (ICU) patients., Methods: Between September 2020 and December 2022, our study enrolled ICU patients diagnosed with stage 3 SA-AKI. We collected demographic information, illness severity indices, and laboratory data, including plasma SCUBE2 and sepsis-triggered cytokine levels. We employed receiver operating characteristic curves and DeLong tests to assess the predictive accuracy for survival, Kaplan-Meier curves to evaluate the relative risk of death, and multivariate logistic regression to identify independent mortality predictors., Results: Among the total of 200 participants, the survivors had significantly higher plasma SCUBE2 levels (115.9 ng/mL) compared to those who died (35.6 ng/mL). SCUBE2 levels showed a positive correlation with the anti-inflammatory cytokine IL-10 and a negative correlation with the APACHE II score, SOFA score, C-reactive protein, and monocyte chemoattractant protein-1. Multivariate analysis revealed that elevated SCUBE2 and IL-10 levels were independently protective against mortality, and associated with the most favorable 30-day survival outcomes., Conclusions: In ICU patients with stage 3 SA-AKI, lower plasma levels of SCUBE2 were correlated with elevated pro-inflammatory factors, which impacted survival outcomes. This suggests that SCUBE2 could be a potential biomarker for predicting prognosis in patients with SA-AKI., (Copyright © 2024. Published by Elsevier B.V.)

Background: Time-dependent changes in cell populations during acute bacterial infections remain unclear. We assessed time-dependent changes in fluorescent light intensity of the neutrophil area (NE-SFL) and fluorescent light distribution width index of the neutrophil area (NE-WY) and their association with sepsis and bacteremia., Methods: Patients with acute bacterial infections were enrolled in this prospective, observational cohort study. Blood samples were collected from all patients at the onset of bacterial infections (day 0) and on days 1 and 3. Microbiological evaluation included the examination of blood bacterial load using PCR. Cell population data were assessed using an automated hematology analyzer (Sysmex series XN-2000)., Results: Forty-three participants with acute bacterial infections were enrolled in the study. Twenty-five participants developed definite sepsis. All the participants improved after the onset of infection. NE-WY levels showed significant time-dependent changes in participants with sepsis, peaking on day 0 and significantly decreasing until day 3, whereas these changes were not statistically significant for NE-SFL. A significant correlation with the Sequential Organ Failure Assessment score was observed with NE-WY and NE-SFL in the entire cohort on days 0 and 1. However, only NE-WY showed a significant correlation with blood bacterial load on days 0 and 1., Conclusion: This study demonstrated that NE-WY elevation in sepsis peaked earlier than NE-SFL, which may partly reflect the early bacterial invasion into circulation. These findings advocate caution in interpreting cell population data values as sepsis biomarkers and propose the potential of NE-WY as a therapeutic indicator., Competing Interests: Declaration of competing interest Hideki Niimi received research funding on a contract basis and joint re-search funding from Sysmex Corporation. Rinako Yoshida and Yosuke Iwasaki were employees of the Sysmex Corporation. The authors declare that this study received funding from Sysmex Corporation. The funder had the following involvement in the study: study design, analysis, interpretation of data. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Sepsis remains a leading cause of death worldwide with no proven immunomodulatory therapies. Stratifying Patient Immune Endotypes in Sepsis ('SPIES') is a prospective, multicenter observational study testing the utility of ELISpot as a functional bioassay specifically measuring cytokine-producing cells after stimulation to identify the immunosuppressed endotype, predict clinical outcomes in septic patients, and test potential immune stimulants for clinical development. Most ELISpot protocols call for the isolation of PBMC prior to their inclusion in the assay. In contrast, we developed a diluted whole blood (DWB) ELISpot protocol that has been validated across multiple laboratories. Heparinized whole blood was collected from healthy donors and septic patients and tested under different stimulation conditions to evaluate the impact of blood dilution, stimulant concentration, blood storage, and length of stimulation on ex vivo IFNγ and TNFα production as measured by ELISpot. We demonstrate a dynamic range of whole blood dilutions that give a robust ex vivo cytokine response to stimuli. Additionally, a wide range of stimulant concentrations can be utilized to induce cytokine production. Further modifications demonstrate anticoagulated whole blood can be stored up to 24 h at room temperature without losing significant functionality. Finally, we show ex vivo stimulation can be as brief as 4 h allowing for a substantial decrease in processing time. The data demonstrate the feasibility of using ELISpot to measure the functional capacity of cells within DWB under a variety of stimulation conditions to inform clinicians on the extent of immune dysregulation in septic patients., Competing Interests: Declaration of competing interest M.B.M., K.E.R., and I.R.T. are members of Immune Functional Diagnostics, LLC (IFDx LLC) and receive no direct financial compensation. IFDx LLC is developing predictive metrics in critical illness and this technology is evaluated in this research. S.C·B, L.L.M., R.S.H., and the University of Florida may receive royalty income based on a technology developed by S.C.B. and others and licensed by Washington University in St. Louis to IFDx LLC. That technology is evaluated in this research. C.C.C. and the University of Cincinnati may receive royalty income based on a technology developed by C.C.C. and others and licensed by Washington University in St. Louis to IFDx LLC. That technology is evaluated in this research., (Published by Elsevier B.V.)

Sepsis remains a significant global health burden and contributor to mortality, yet the precise molecular mechanisms underlying the immune response are not fully elucidated. To gain insight into this issue, we performed a comprehensive analysis using a variety of techniques including bulk RNA sequencing, single-cell RNA sequencing, and enzyme-linked immunosorbent assay (ELISA). We performed enrichment analysis of differentially expressed genes in sepsis and healthy individuals by utilizing Gene Ontology (GO) analysis and indicated significant enrichment of immune-related response. Following Weighted Gene Co-Expression Network Analysis (WGCNA) and protein-protein interaction analysis (PPI) were used to identify key immune-related hub genes and validated by ELISA to show that NLRC4 is highly expressed in sepsis. Additionally, an analysis of scRNA-seq data from newly diagnosed sepsis, sepsis diagnosis at 6 hours, and healthy samples demonstrates a significant increase in both the expression levels and proportions of NLRC4 in sepsis monocytes and neutrophils. In addition, using pySCENIC we identified upstream transcription factors that regulate NLRC4. Our study provides valuable insights into the identification of NLRC4 in peripheral blood as a potential candidate gene for the diagnosis and treatment of sepsis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: Blood level of pancreatic stone protein (PSP) is a promising biomarker of sepsis both in adults and children. The aim of our study was to investigate the diagnostic accuracy of PSP in children with suspected sepsis and to compare diagnostic performance with other sepsis biomarkers approved for clinical use, that is, procalcitonin (PCT) and C-reactive protein (CRP)., Design: Prospective study., Setting: PICU and pediatric emergency department., Intervention: Blood levels of PSP were measured using a nanofluidic point-of-care immunoassay (abioSCOPE, Abionic SA, Switzerland) within 24 hours of admission., Measurements and Main Results: We studied 99 children aged between older than 1 month and younger than 18 years with signs and symptoms of systemic inflammatory response syndrome (irrespective of associated organ dysfunction). The prevalence of sepsis was 35 of 99 (35.4%). Patients with sepsis had higher PSP levels ( p < 0.001) than patients with systemic inflammation of noninfectious cause. In this analysis, the optimal cutoff for the diagnosis of sepsis using PSP was 123 ng/mL, which resulted in a sensitivity of 0.63 (95% CI, 0.43-0.80), specificity of 0.89 (95% CI, 0.77-0.95). The PSP test area under the receiver operating characteristic curve (AUROC) was 0.82 (95% CI, 0.73-0.91) and, by comparison, procalcitonin and CRP AUROC were 0.70 (95% CI, 0.58-0.82) and 0.72 (95% CI, 0.60-0.84), respectively. Overall, the pretest to posttest probability of sepsis with a positive test changed from 0.35 to 0.73., Conclusions: In this single-center prospective pediatric cohort, admitted to the high intensive care and to the PICU, our findings suggested the potential use of PSP as a sepsis biomarker. However, because of the clinical diagnostic uncertainty with a positive result, further investigation is needed particularly in combination with other biomarkers., Competing Interests: Dr. Cecchetti received support for article research from the National Institutes of Health; he disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: In sepsis treatment, antibiotics are crucial, but overuse risks development of antibiotic resistance. Recent guidelines recommended the use of procalcitonin to guide antibiotic cessation, but solid evidence is insufficient. Recently, concerns were raised that this strategy would increase recurrence. Additionally, optimal protocol or difference from the commonly used C-reactive protein (CRP) are uncertain. We aimed to compare the effectiveness and safety of procalcitonin- or CRP-guided antibiotic cessation strategies with standard of care in sepsis., Data Sources: A systematic search of PubMed, Embase, CENTRAL, Igaku Chuo Zasshi, ClinicalTrials.gov , and World Health Organization International Clinical Trials Platform., Study Selection: Randomized controlled trials involving adults with sepsis in intensive care., Data Extraction: A systematic review with network meta-analyses was performed. The Grading of Recommendations, Assessments, Developments, and Evaluation method was used to assess certainty., Data Synthesis: Eighteen studies involving 5023 participants were included. Procalcitonin-guided and CRP-guided strategies shortened antibiotic treatment (-1.89 days [95% CI, -2.30 to -1.47], -2.56 days [95% CI, -4.21 to -0.91]) with low- to moderate-certainty evidence. In procalcitonin-guided strategies, this benefit was consistent even in subsets with shorter baseline antimicrobial duration (7-10 d) or in Sepsis-3, and more pronounced in procalcitonin cutoff of "0.5 μg/L and 80% reduction." No benefit was observed when monitoring frequency was less than half of the initial 10 days. Procalcitonin-guided strategies lowered mortality (-27 per 1000 participants [95% CI, -45 to -7]) and this was pronounced in Sepsis-3, but CRP-guided strategies led to no difference in mortality. Recurrence did not increase significantly with either strategy (very low to low certainty)., Conclusions: In sepsis, procalcitonin- or CRP-guided antibiotic discontinuation strategies may be beneficial and safe. In particular, the usefulness of procalcitonin guidance for current Sepsis-3, where antimicrobials are used for more than 7 days, was supported. Well-designed studies are needed focusing on monitoring protocol and recurrence., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objective: Biomarkers with high accuracy for identification of infection in decompensated chronic liver disease (DCLD) are urgently needed. We compared the accuracy of neutrophilic cluster of differentiation 64 (nCD64) with procalcitonin for diagnosis of bacterial infection in children with DCLD., Methods: Consecutive children admitted with DCLD were enrolled prospectively. nCD64 was assessed by flow cytometry and expressed in percentage. nCD64, procalcitonin and hemogram were measured at admission and 7-14 days after treatment in those with infection. Complete work-up for infection was done. Presence, site and severity of infection was classified as per guidelines., Results: 107 children [64 boys, age 97(18-168) months] were enrolled. 78(72.9%) had infection, 26(24%) had severe sepsis and 60(56%) had systemic inflammatory response syndrome. The commonest site of infection was ascitic fluid (n=37), followed by pneumonia (n=24), urinary tract (n=15), bacteraemia (n=10), cholangitis (n=8) and cellulitis (n=3). nCD64 (cut-off-51%, AUC-0.82) had a higher sensitivity (79.5%) and specificity (82.8%) than procalcitonin (cut-off ≥0.58ng/mL, AUC-0.74, sensitivity-76.9% and specificity-62.1%) for diagnosis of infection. nCD64 and procalcitonin correlated with infection severity, being highest in children with severe sepsis [88(71-97) %and 1.98(0.83-10.36) ng/mL], than in infection alone [72(45-84) % and 1.09(0.45-2.07) ng/mL], and no-infection [36(20.2-48) % and 0.42(0.19-1.08) ng/mL]. There was no difference in diagnostic utility of procalcitonin or nCD64 with different sites of infection. Elevation of all 3 parameters (nCD64, PCT and total leukocyte count) was uncommon but highly specific for presence of infection., Conclusion: nCD64 identifies infection better than procalcitonin and correlates well with infection severity in children with DCLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

A lactate/albumin ratio (LAR) greater than 0.5 measured early in the course of pediatric critical illness is associated with greater mortality. Whether the elevated LAR can be explained by microcirculation disorders in children with sepsis is not known. In this longitudinal retrospective study (January 2021-January 2024), serum albumin and lactate were measured on admission to the pediatric intensive care unit (PICU), with sublingual video microscopy performed simultaneously to measure microcirculation. A total of 178 children were included, 37% of whom had septic shock measured with the Phoenix Sepsis Score. Patients with remote sepsis had greater odds of an elevated LAR (aOR 6.87: 95% CI 1.98-23.73; p < 0.01). Children with an elevated LAR had more microvascular blood flow abnormalities (aOR 1.31 95% CI 1.08-1.58; p < 0.01), lower 4-6-micron capillary density (aOR 1.03 95% CI 1.01-1.05; p < 0.01) and greater odds of dying (aOR 3.55 95% CI 1.21-10.38; p = 0.02) compared to those with a low LAR. We found no association between LAR and endothelial glycocalyx degradation. A normal LAR is associated with less risk of microcirculatory injury (aOR 0.77 95% CI 0.65-0.93; p < 0.01). In children with sepsis, an elevated LAR is associated with microcirculation abnormalities (microvascular density and flow). The lactate/albumin ratio is a potentially useful biomarker for microcirculatory injury in sepsis., (© 2024. The Author(s).)