BACKGROUND: The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis. In this study, we aim to introduce a model to describe and monitor the immune status of sepsis and to explore its prognostic value.

METHODS: A prospective observational study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between July 2016 and December 2018. Blood samples were collected at days 1 and 3. Serum cytokine levels (e.g., tumor necrosis factor-α [TNF-α], interleukin-10 [IL-10]) and CD14⁺ monocyte human leukocyte antigen-D-related (HLA-DR) expression were measured to serve as immune markers. Classification of each immune status, namely systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS), and mixed antagonistic response syndrome (MARS), was defined based on levels of immune markers. Changes of immune status were classified into four groups which were stabilization (SB), deterioration (DT), remission (RM), and non-remission (NR).

RESULTS: A total of 174 septic patients were enrolled including 50 non-survivors. Multivariate analysis discovered that IL-10 and HLA-DR expression levels at day 3 were independent prognostic factors. Patients with MARS had the highest mortality rate. Immune status of 46.1% patients changed from day 1 to day 3. Among four groups of immune status changes, DT had the highest mortality rate, followed by NR, RM, and SB with mortality rates of 64.7%, 42.9%, and 11.2%, respectively.

CONCLUSIONS: Severe immune disorder defined as MARS or deterioration of immune status defined as DT lead to the worst outcomes. The preliminary model of the classification and dynamic monitoring of immune status based on immune markers has prognostic values and is worthy of further investigation.

BACKGROUND: The study aims to investigate the performance of a metagenomic next-generation sequencing (NGS)-based diagnostic technique for the identification of potential bacterial and viral infections and effects of concomitant viral infection on the survival rate of intensive care unit (ICU) sepsis patients.

METHODS: A total of 74 ICU patients with sepsis who were admitted to our institution from February 1, 2018 to June 30, 2019 were enrolled. Separate blood samples were collected from patients for blood cultures and metagenomic NGS when the patients’ body temperature was higher than 38 °C. Patients’ demographic data, including gender, age, ICU duration, ICU scores, and laboratory results, were recorded. The correlations between pathogen types and sepsis severity and survival rate were evaluated.

RESULTS: NGS produced higher positive results (105 of 118; 88.98%) than blood cultures (18 of 118; 15.25%) over the whole study period. Concomitant viral infection correlated closely with sepsis severity and had the negative effect on the survival of patients with sepsis. However, correlation analysis indicated that the bacterial variety did not correlate with the severity of sepsis.

CONCLUSIONS: Concurrent viral load correlates closely with the severity of sepsis and the survival rate of the ICU sepsis patients. This suggests that prophylactic administration of antiviral drugs combined with antibiotics may be beneficial to ICU sepsis patients.

BACKGROUND: Sepsis is a common cause of death in emergency departments and sepsis-associated encephalopathy (SAE) is a major complication. Rosuvastatin may play a neuroprotective role due to its protective effects on the vascular endothelium and its anti-inflammatory functions. Our study aimed to explore the potential protective function of rosuvastatin against SAE.

METHODS: Sepsis patients without any neurological dysfunction on admission were prospectively enrolled in the “Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome” study (SAILS trial, ClinicalTrials.gov number: NCT00979121). Patients were divided into rosuvastatin and placebo groups. This is a secondary analysis of the SAILS dataset. Baseline characteristics, therapy outcomes, and adverse drug events were compared between groups.

RESULTS: A total of 86 patients were eligible for our study. Of these patients, 51 were treated with rosuvastatin. There were significantly fewer cases of SAE in the rosuvastatin group than in the placebo group (32.1% vs. 57.1%, P=0.028). However, creatine kinase levels were significantly higher in the rosuvastatin group than in the placebo group (233 [22-689] U/L vs. 79 [12-206] U/L, P=0.034).

CONCLUSION: Rosuvastatin appears to have a protective role against SAE but may result in a higher incidence of adverse events.

BACKGROUND: Intestinal microcirculation dysfunction is an important factor that causes poor prognosis in sepsis patients and is an important pathophysiological basis for the occurrence and development of sepsis.

DATA RESOURCES: PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched from inception to August 1, 2021. The search was limited to the English language only. Two reviewers independently identified studies related to intestinal microcirculation dysfunction in sepsis. Exclusion criteria were duplicate articles according to multiple search criteria.

RESULTS: Fifty articles were included, and most of them were animal studies. These studies reported pathogenesis, including endothelial dysfunction, leukocyte recruitment and adhesion, microthrombus formation, microcirculation hypoperfusion, and redistribution of intestinal wall blood flow. The monitoring methods of intestinal microcirculation were also diverse, including handheld microscopes, intravital microscopy (IVM), laser Doppler blood flow instruments, laser speckle contrast imaging, tissue reflectance spectrophotometry, biochemical markers of intestinal ischemia, and histopathological examination. In view of the related pathogenesis of intestinal microcirculation disorder in sepsis, existing studies also have different opinions on its treatment.

CONCLUSIONS: Limited by monitoring, there are few clinical studies on intestinal microcirculation dysfunction in sepsis. Related research mainly focuses on basic research, but some progress has also been made. Therefore, this review may provide a reference for future research on intestinal microcirculation dysfunction in sepsis.

BACKGROUND: The aim of the study was to investigate the procalcitonin-to-cortisol ratio (P/C ratio) as a prognostic predictor among septic patients with abdominal source.

METHODS: We retrospectively enrolled 132 post-surgery patients between 18 and 90 years old with sepsis of the abdominal source. On the second day of sepsis onset, cortisol, procalcitonin (PCT), Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, C-response protein (CRP), and other baseline characteristics were collected. In addition, the length of ICU stay, length of mechanical ventilation (MV) days, length of shock days, and 28-day mortality were also recorded. Univariate analysis was performed to screen potential risk factors. Stratified analysis was used to identify the interaction among the risk factors. Multivariate analysis was also utilized to demonstrate the relationship between the risk factors and mortality. The receiver operator characteristic (ROC) curve analysis was conducted to evaluate the risk factors. A restricted cubic spline (RCS) demonstrated the association between survival outcome and the P/C ratio variation.

RESULTS: A total of twenty-nine patients died, and 103 patients survived within 28 d. There were significant differences in cortisol, PCT, P/C ratio, interleukin (IL)-6, SOFA, and APACHE II scores between the survival and non-survival groups. No significant interaction was observed in the stratified analysis. Logistic regression analysis revealed that P/C ratio (P=0.033) was significantly related to 28-day mortality. Based on ROC curves, P/C ratio (AUC=0.919) had a higher AUC value than cortisol or PCT. RCS analysis depicted a positive relationship between survival possibility and P/C ratio decrement.

CONCLUSION: P/C ratio might be a potential prognostic predictor in septic patients with abdominal sources.

BACKGROUND: The latest sepsis definition includes both infection and organ failure, as evidenced by the sequential organ failure assessment (SOFA) score. However, the applicability of the pediatric SOFA score (pSOFA) is not yet determined. This study evaluated the effectiveness of both pSOFA and system inflammatory reaction syndrome (SIRS) scores in predicting sepsis-related pediatric deaths.

METHODS: This is a retrospective multi-center cohort study including hospitalized patients <18 years old with diagnosed or not-yet-diagnosed infections. Multivariate analyses were carried out to evaluate risk factors for in-hospital mortality. According to Youden index (YI), three sub-categories of pSOFA were screened out and a new simplified pSOFA score (spSOFA) was formed. The effectiveness and accuracy of prediction of pSOFA, SIRS and spSOFA was retrieved from the area under the receiver operating characteristic curve (AUROC) and Delong’s test.

RESULTS: A total of 1,092 participants were eligible for this study, and carried a 23.4% in-hospital mortality rate. The 24-h elevated pSOFA score (24 h-pSOFA), bloodstream infection, and mechanical ventilation (MV) requirement were major risk factors associated with sepsis-related deaths. The AUROC analysis confirmed that the spSOFA provided good predictive capability in sepsis-related pediatric deaths, relative to the 24 h-pSOFA and SIRS.

CONCLUSIONS: The pSOFA score performed better than SIRS in diagnosing infected children with high mortality risk. However, it is both costly and cumbersome. We, therefore, proposed spSOFA to accurately predict patient outcome, without the disadvantages. Nevertheless, additional investigations, involving a large sample population, are warranted to confirm the conclusion of this study.

BACKGROUND: Patients with sepsis often exhibit an acute inflammatory response, followed by an immunosuppressive phase with a poor immune response. However, the underlying mechanisms have not been fully elucidated.

METHODS: We sought to comprehensively characterize the transcriptional changes in neutrophils of patients with sepsis by transcriptome sequencing. Additionally, we conducted a series of experiments, including real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry to investigate the role of arginase-1 signaling in sepsis.

RESULTS: Through the analysis of gene expression profiles, we identified that the negative regulation of T cell activation signaling was enriched, and the expression of arginase-1 was high in neutrophils from patients with sepsis. Furthermore, we conducted flow cytometry and found that the function of CD8⁺ T cells in septic patients was impaired. Moreover, neutrophils from septic patients inhibited the percentage of polyfunctional effector CD8⁺ T cells through arginase-1. Additionally, the proportions of granzyme B⁺IFN^-γ⁺CD8⁺ T and TNF^-α⁺IFN^-γ⁺CD8⁺ T cells increased after inhibition of arginase-1 signaling.

CONCLUSION: The impaired effector function of CD8⁺ T cells could be restored by blocking arginase-1 signaling in patients with sepsis.

BACKGROUND: Septic cardiomyopathy (SCM) occurs in the early stage of sepsis and septic shock, which has implications for treatment strategies and prognosis. Additionally, myocardial involvement in the early stages of sepsis is difficult to identify. Here, we assess subclinical myocardial function using laboratory tests and speckle-tracking echocardiography (STE).

METHODS: Emergency department patients diagnosed with sepsis or septic shock were included for analysis. Those with other causes of acute or pre-existing cardiac dysfunction were excluded. Transthoracic echocardiography (TTE), including conventional echocardiography and STE, were performed for all patients three hours after initial resuscitation. Samples for laboratory tests were taken around the time of TTE.

RESULTS: Left ventricular functions of 60 patients were analyzed, including 21 septic shock patients and 39 sepsis patients. There was no significant difference in global longitudinal strain (GLS), global circumferential strain (GCS), or global radical strain (GRS) between patients with sepsis and septic shock (all with P>0.05). However, GLS and GCS were significantly less negative in patients with abnormal troponin levels or in patients with abnormal left ventricular ejection fraction (LVEF) values (all with P<0.05). There were also moderate correlations between GLS and levels of cTnI (r=0.40, P=0.002) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r=0.44, P=0.001) in sepsis and septic shock patients.

CONCLUSION: Myocardial dysfunction, e.g., lower LVEF or less negative GLS in patients with sepsis or septic shock, is more affected by myocardial injury. GLS could be incorporated into mainstream clinical practice as a supplementary LVEF parameter, especially for those with elevated troponin levels.

BACKGROUND: The quick sequential organ failure assessment (qSOFA) is recommended to identify sepsis and predict sepsis mortality. However, some studies have recently shown its poor performance in sepsis mortality prediction. To enhance its effectiveness, researchers have developed various revised versions of the qSOFA by adding other parameters, such as the lactate-enhanced qSOFA (LqSOFA), the procalcitonin-enhanced qSOFA (PqSOFA), and the modified qSOFA (MqSOFA). This study aimed to compare the performance of these versions of the qSOFA in predicting sepsis mortality in the emergency department (ED).
METHODS: This retrospective study analyzed data obtained from an electronic register system of adult patients with sepsis between January 1 and December 31, 2019. Receiver operating characteristic (ROC) curve analyses were performed to determine the area under the curve (AUC), with sensitivity, specificity, and positive and negative predictive values calculated for the various scores.
RESULTS: Among the 936 enrolled cases, there were 835 survivors and 101 deaths. The AUCs of the LqSOFA, MqSOFA, PqSOFA, and qSOFA were 0.740, 0.731, 0.712, and 0.705, respectively. The sensitivity of the LqSOFA, MqSOFA, PqSOFA, and qSOFA were 64.36%, 51.40%, 71.29%, and 39.60%, respectively. The specificity of the four scores were 70.78%, 80.96%, 61.68%, and 91.62%, respectively. The LqSOFA and MqSOFA were superior to the qSOFA in predicting in-hospital mortality.
CONCLUSIONS: Among patients with sepsis in the ED, the performance of the PqSOFA was similar to that of the qSOFA and the values of the LqSOFA and MqSOFA in predicting in-hospital mortality were greater compared to qSOFA. As the added parameter of the MqSOFA was more convenient compared to the LqSOFA, the MqSOFA could be used as a candidate for the revised qSOFA to increase the performance of the early prediction of sepsis mortality.

BACKGROUND: This study aims to evaluate the effect of continuous renal replacement therapy (CRRT) on inflammation-related anemia, iron metabolism, and the prognosis in sepsis patients with acute kidney injury (AKI).

METHODS: Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups. The clinical and laboratory data on days 1, 3 and 7 after intensive care unit (ICU) admission were collected. The serum interleukin (IL)-6, hepcidin, erythropoietin, ferritin, and soluble transferrin receptor (sTfR) were determined by enzyme-linked immunosorbent assay. The Sequential Organ Failure Assessment (SOFA) score and 28-day mortality were recorded. Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test (categorical variables), and Mann-Whitney U-test or t-test (continuous variables).

RESULTS: The hemoglobin and serum erythropoietin levels did not significantly differ between the CRRT and control groups though gradually decreased within the first week of ICU admission. On days 3 and 7, the serum IL-6, hepcidin, ferritin, and red blood cell distribution width significantly decreased in the CRRT group compared to the control group (all P<0.05). On day 7, the serum iron was significantly elevated in the CRRT group compared to the control group (P<0.05). However, the serum sTfR did not significantly differ between the groups over time. In addition, the SOFA scores were significantly lower in the CRRT group compared to the control group on day 7. The 28-day mortality did not significantly differ between the control and CRRT groups (38.0% vs. 28.2%, P=0.332).

CONCLUSION: CRRT might have beneficial effects on the improvement in inflammation-related iron metabolism and disease severity during the first week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.

BACKGROUND: This study aimed to explore the changes of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) expression on antigen-presenting cells (APCs) and evaluate their association with organ failure and mortality during early sepsis.

METHODS: In total, 40 healthy controls and 198 patients with sepsis were included in this study. Peripheral blood was collected within the first 24 h after the diagnosis of sepsis. The expression of PD-L1 and PD-1 was determined on APCs, such as B cells, monocytes, and dendritic cells (DCs), by flow cytometry. Cytokines in plasma, such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, and IL-17A were determined by Luminex assay.

RESULTS: PD-1 expression decreased significantly on B cells, monocytes, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs) as the severity of sepsis increased. PD-1 expression was also markedly decreased in non-survivors compared with survivors. In contrast, PD-L1 expression was markedly higher on mDCs, pDCs, and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors. The PD-L1 expression on APCs (monocytes and DCs) was weakly related to organ dysfunction and inflammation. The area under the receiver operating characteristic curve (AUC) of the PD-1 percentage of monocytes (monocyte PD-1%)+APACHE II model (0.823) and monocyte PD-1%+SOFA model (0.816) had higher prognostic value than other parameters alone. Monocyte PD-1% was an independent risk factor for 28-day mortality.

CONCLUSION: The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs. PD-L1 in monocytes and DCs was weakly correlated with inflammation and organ dysfunction during early sepsis. The combination of SOFA or APACHE II scores with monocyte PD-1% could improve the prediction ability for mortality.

BACKGROUND: Endothelial dysfunction in sepsis is a pathophysiological feature of septic organ failure. Endothelial cells (ECs) exhibit specific metabolic traits and release metabolites to adapt to the septic state in the blood to maintain vascular homeostasis.

METHODS: Web of Science and PubMed were searched from inception to October 1, 2022. The search was limited to the English language only. Two reviewers independently identified studies related to EC metabolism in sepsis. The exclusion criteria were duplicate articles according to multiple search criteria.

RESULTS: Sixty articles were included, and most of them were cell and animal studies. These studies reported the role of glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism in EC homeostasis. including glycolysis, oxidative phosphorylation, fatty acid metabolism and amino acid metabolism. However, dysregulation of EC metabolism can contribute to sepsis progression.

CONCLUSION: There are few clinical studies on EC metabolism in sepsis. Related research mainly focuses on basic research, but some scientific problems have also been clarified. Therefore, this review may provide an overall comprehension and novel aspects of EC metabolism in sepsis.