Complication Of Sepsis Research Articles

The impact of glucose metabolism on inflammatory processes in sepsis-induced acute lung injury

Acute lung injury (ALI) is a prevalent and critical complication of sepsis, marked by high incidence and mortality rates, with its pathogenesis still not being fully elucidated. Recent research has revealed a significant correlation between the metabolic reprogramming of glucose and sepsis-associated ALI (S-ALI). Throughout the course of S-ALI, immune cells, including macrophages and dendritic cells, undergo metabolic shifts to accommodate the intricate demands of immune function that emerge as sepsis advances. Indeed, glucose metabolic reprogramming in S-ALI serves as a double-edged sword, fueling inflammatory immune responses in the initial stages and subsequently initiating anti-inflammatory responses as the disease evolves. In this review, we delineate the current research progress concerning the pathogenic mechanisms linked to glucose metabolic reprogramming in S-ALI, with a focus on the pertinent immune cells implicated. We encapsulate the impact of glucose metabolic reprogramming on the onset, progression, and prognosis of S-ALI. Ultimately, by examining key regulatory factors within metabolic intermediates and enzymes, We have identified potential therapeutic targets linked to metabolic reprogramming, striving to tackle the inherent challenges in diagnosing and treating Severe Acute Lung Injury (S-ALI) with greater efficacy.

Identification and verification of feature biomarkers associated with choline metabolism in sepsis-induced cardiomyopathy.

Background: Sepsis-induced cardiomyopathy (SIC), one of the most common complications of sepsis, seriously affects the prognosis of critically ill patients. Choline metabolism is an important biological process in the organism, and the mechanism of its interaction with SIC is unclear. The aim of this study was to reveal the choline metabolism genes (CMGs) associated with SIC and to provide effective targets for the treatment of SIC.Methods: Through a comprehensive analysis of the microarray dataset GSE79962 (comprising 20 SIC patients and 11 healthy controls) from the GEO database, suspected co-expression modules and differentially expressed genes (DEGs) in SIC were identified. Hub CMGs were obtained by intersecting choline metabolism database with DEGs and key model genes. Afterward, hub CMGs most significantly involved in prognosis were further analyzed for the verification of major pathways of enrichment analysis. Finally, the expression of hub CMGs in in vivo and in vitro SIC model was verified by immunohistochemistry staining and quantitative real-time polymerase chain reaction analysis (qPCR).Results: WGCNA identified 1 hub gene panel and 3867 hub genes, which were intersected with DEGs and CMGs to obtain the same 3 hub CMGs:HIF-1α, DGKD and PIK3R1. Only HIF-1α shows significant association with mortality (P = 0.009). Subsequent differential analysis based on the high and low HIF-1α expression yielded 63 DEGs and then they were uploaded into Cytoscape software to construct a protein-protein interaction (PPI) network and 6 hub genes with the highest priority were obtained (CISH, THBS1, IMP1, MYC, SOCS3 and VCAN). Finally, a multifactorial COX analysis revealed a significant correlation between HIF-1α and survival in SIC patients, which was further validated by in vitro and in vivo experiments.Conclusion: Our findings will provide new insights into the pathogenesis of SIC, and HIF-1α may have important applications as a potential biomarker for early detection and therapeutic intervention in SIC.

Evaluation of early extubation in the operating room for paediatric patients after congenital open-heart surgery.

Advances in surgical and perioperative care have reduced the need for prolonged mechanical ventilation in children following cardiac surgery. To evaluate the feasibility and assess the clinical outcomes of an early extubation strategy in the operating room for children undergoing congenital heart surgery, including neonates (age < 28 days). This is a retrospective analysis including congenital open-heart surgery cases. We excluded patients who remained open chest postoperatively or patients with severe hemodynamic instability and high inotropic support from the study. Study variables include age, gender, weight, preoperative cardiac diagnosis, preoperative diagnosis of genetic or chromosomal abnormalities, prematurity, preoperative mechanical ventilation (invasive or non-invasive), cardiopulmonary bypass time, circulatory arrest time, postoperative use of inotropes, duration of mechanical ventilation, postoperative respiratory complication, sepsis, bleeding or other complications, paediatric cardiac ICU stay, total hospital stay, incidence of failed extubation, and operative or postoperative mortality. This study included 163 patients who underwent congenital open cardiac surgery, out of these studied patients, 118 (72.4%) were extubated in the operating room. In total, 19.6% of studied patients had Down syndrome. Other genetic or chromosomal disorders were present among 8.6% of studied patients. There was a statistically significant difference between operating room extubation group and non-operating room extubation group regarding Risk Adjustment for Congenital Heart Surgery Score classification, postoperative paediatric ICU duration, postoperative hospital length of stay, vasoactive-inotrope score, duration of inotrope, open chest, and mortality. Extubation in the operating room after congenital open-heart surgery was successful in most of our patients, even following complex procedures.

Effect of stellate ganglion block on perioperative myocardial injury following thoracoscopic surgery for lung cancer (SGBMI): protocol for a single-centre, randomised controlled trial

IntroductionMyocardial injury is a common complication of thoracoscopic surgery. The stellate ganglion block is believed to affect myocardial oxygen consumption. The Stellate Ganglion Block and Myocardial Injury (SGBMI) trial aims...

Interleukin-10: Genetic and biochemical prediction of sepsis-induced acute kidney injury in critically ill patients in intensive care unit: A cross-sectional study.

Sepsis is a potentially life-threatening condition that eventually causes multiorgan dysfunction in critically ill patients. Acute kidney injury (AKI) is a severe life-threatening complication of sepsis, a condition termed sepsis-induced AKI (S-AKI), with poor clinical outcomes and high mortality rates. Inflammatory and immunological responses are important variables in S-AKI. This study aimed to examine the relationship of rs1518111 polymorphism in the interleukin-10 ( IL-10 ) gene and serum/urine IL-10 levels with sepsis-induced AKI in critically ill patients in the intensive care unit (ICU). In this cross-sectional study, 310 critically ill adult patients were recruited, of whom, 197 developed S-AKI. Real-time polymerase chain reaction was performed to detect the rs1518111 polymorphism. Circulating blood and urine IL-10 levels of IL-10 were measured. For rs1518111 SNP, the presence of at least one T allele increased the risk of occurrence of S-AKI (odds ratio [OR]: 1.34, 95% CI: 1.07-3.17; p < 0.001), regardless of the type of infection and severity of sepsis. Blood and urine IL-10 levels were an excellent prediction of S-AKI (area under the receiver operating characteristic curve [AUC]: 0.881 and 0.953 and sensitivity: 90.2% and 97.6% at cutoff of 133.5 and 5.67 pg/mL, respectively). Regression analysis showed that white blood cell count and increased blood and urine IL-10 levels, in addition to the presence of TT genotype, are independent risk factors for S-AKI. rs1518111 polymorphism in the IL-10 gene is a risk factor for sepsis-induced AKI in the ICU. Serum/urine IL-10 levels may be used as predictors of S-AKI in critically ill patients with sepsis, thereby improving early management.

ROS responsive nanozyme loaded with STING silencing for the treatment of sepsis-induced acute lung injury

Acute lung injury (ALI) is a common complication of sepsis and a leading cause of mortality in septic patients. Studies indicate that STING may play a crucial role in the pathogenesis of sepsis-induced ALI by interacting with the PARP-1/NLRP3 pathway. Therefore, targeting STING inhibition has potential as a novel therapeutic strategy for ALI. However, effective inhibition remains challenging due to the widespread expression of STING across various tissues. In this study, we developed a nanozyme-based drug delivery system, DSPE-TK-mPEG-MnO2@siSTING (abbreviated as DTmM@siSTING), using DSPE-TK-mPEG-MnO2 as the carrier, and characterized it via scanning electron microscopy, dynamic light scattering, nanoparticle size analysis, and gel electrophoresis. To evaluate the therapeutic effects of DTmM@siSTING, an in vitro ALI cell model and an in vivo ALI mouse model were established, assessing the nanozyme's impact on ROS levels, inflammatory responses, and the PARP-1/NLRP3 pathway in sepsis-induced ALI. Results demonstrated that DTmM@siSTING exhibited good physiological stability. In vitro, DTmM@siSTING significantly reduced ROS levels, myeloperoxidase activity, and expression of inflammatory cytokines, while also inhibiting PARP-1/NLRP3 pathway activation. In vivo experiments further revealed that DTmM@siSTING effectively delivered siSTING to the lungs, mitigating sepsis-induced ALI and associated inflammatory responses. Additionally, DTmM@siSTING displayed excellent biocompatibility. In summary, our findings suggest that DTmM@siSTING significantly enhances the therapeutic efficacy of siSTING, alleviating ALI by inhibiting ROS production, inflammatory responses, and activation of the PARP-1/NLRP3 pathway. This novel approach presents a promising therapeutic avenue for sepsis-induced ALI.

Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Mitigates Neuroinflammation and Cognitive Impairment by Modulating Glial Activation in Sepsis-Associated Encephalopathy.

Sepsis-associated encephalopathy (SAE) is a severe neurological complication of sepsis, characterized by cognitive impairment and increased mortality. Owing to the established neuroprotective and immunomodulatory effects of Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) in a plethora of neurological disorders, our study aimed to investigate the role of MANF in SAE and evaluate its potential as a therapeutic target. Employing a cecal ligation and puncture (CLP) mouse model of sepsis, we analyzed MANF expression in the hippocampus and cortex, and evaluated the influence of intranasally administered recombinant human MANF (rhMANF) on symptoms of SAE. Our results disclosed a substantial increase in MANF protein levels within the hippocampus and cortex of septic mice, primarily found in neurons. Post-CLP surgical administration of rhMANF led to numerous favorable outcomes. Specifically, rhMANF therapy mitigated sepsis-induced behavioral deviations and cognitive impairments, as gauged by SHIRPA scores and Morris water maze tests, and enhanced survival rates in septic mice. These enhancements were concomitant with alterations in neuroinflammation and synaptic integrity. The rhMANF treatment attenuated activation of microglia and astrocytes in the hippocampus and cortex, as evidenced by diminished Iba-1 and GFAP positive cells. It also curtailed the generation of pro-inflammatory cytokines TNF-α and IL-6, and obstructed the p38 MAPK inflammatory pathway. Moreover, rhMANF sustained the expression of synaptic proteins PSD95 and SYN, and conserved neuronal integrity, as demonstrated by Nissl staining. In conclusion, our study underscores the potential of MANF as an innovative therapeutic target for SAE, emphasizing its anti-inflammatory and neuroprotective capabilities.

Sepsis-associated liver injury: Mechanisms and potential therapeutic targets

In this editorial, we examined a recent article in the World Journal of Gastroenterology that focused on sepsis-associated liver injury (SLI) and its treatment. SLI is a serious complication of sepsis, primarily caused by microcirculatory disturbances, the gut-liver axis, and inflammatory responses. Specific treatment recommendations for SLI are lacking. The gut-liver axis represents a potential therapeutic target, with metformin showing promise in modulating the gut microbiome and enhancing intestinal barrier function. Although immunomodulatory therapies are being explored, anti-tumor necrosis factor agents and interleukin-1 receptor antagonists have not demonstrated significant clinical benefits. Statins may reduce liver inflammation and prevent injury in sepsis, but their clinical application is limited. Reduced D-related human leucocyte antigen expression on monocytes and lymphocytes suggests immune suppression in patients, indicating that corticosteroids could reverse clinical deterioration in severe infections and address adrenal cortical insufficiency. Current large-scale studies on glucocorticoid therapy for sepsis have yielded mixed results, likely due to inadequate assessment of the immune status of the host. Future research should prioritize the development of personalized immunotherapy tailored to patients’ immune profiles, focusing on identifying novel indicators of immune status and advancing immunomodulatory targets and therapeutics for septic patients.

TSPO exacerbates sepsis-induced cardiac dysfunction by inhibiting p62-Mediated autophagic flux via the ROS-RIP1/RIP3-exosome axis

Septic cardiomyopathy (SCM) is a critical complication of sepsis, primarily attributed to mitochondrial dysfunction and impaired autophagic flux. This study explores the role of translocator protein (TSPO) in SCM pathogenesis and assesses its potential as a therapeutic target. We identified increased TSPO expression in plasma samples from sepsis patients, with further validation in septic rats and LPS-stimulated H9C2 cardiomyocytes. Elevated TSPO disrupted mitochondrial function, leading to increased reactive oxygen species (ROS) production and activation of the RIP1/RIP3 pathway, which hindered p62-positive autophagosome degradation and promoted inflammation. Moreover, exosome release containing TSPO-positive autophagosomes into plasma may exacerbate systemic inflammation. NADH, identified as a TSPO-binding molecule, restored autophagic flux, improved mitochondrial function, and enhanced cardiac performance and survival in septic rats. These findings suggest that targeting TSPO with NADH could alleviate mitochondrial dysfunction and inflammatory responses in SCM, providing a promising therapeutic strategy for sepsis-induced cardiac injury.

Dexmedetomidine Attenuates Neuroinflammation-Mediated Hippocampal Neurogenesis Impairment in Sepsis-Associated Encephalopathy Mice through Central α2A-Adrenoceptor.

Sepsis-associated encephalopathy (SAE), one of the common complications of sepsis, is associated with higher ICU mortality, prolonged hospitalization, and long-term cognitive decline. Sepsis can induce neuroinflammation, which negatively affects hippocampal neurogenesis. Dexmedetomidine has been shown to protect against SAE. However, the potential mechanism remains unclear. In this study, we added lipopolysaccharide (LPS)-stimulated astrocytes-conditioned media (LPS-CM) to neural stem cells (NSCs) culture, which were pretreated with dexmedetomidine in the presence or absence of the α2-adrenoceptor antagonist yohimbine or the α2A-adrenoceptor antagonist BRL-44408. LPS-CM impaired the neurogenesis of NSCs, characterized by decreased proliferation, enhanced gliogenesis, and declined viability. Dexmedetomidine alleviated LPS-CM-induced impairment of neurogenesis in a dose-dependent manner. Yohimbine, as well as BRL-44408, reversed the effects of dexmedetomidine. We established a mouse model of SAE via cecal ligation and perforation (CLP). CLP-induced astrocyte-related neuroinflammation and hippocampal neurogenesis deficits, accompanied by learning and memory decline, which were reversed by dexmedetomidine. The effect of dexmedetomidine was blocked by BRL-44408. Collectively, our findings support the conclusion that dexmedetomidine can protect against SAE, likely mediated by the combination of inhibiting neuroinflammation via the astrocytic α2A-adrenoceptor with attenuating neuroinflammation-induced hippocampal neurogenesis deficits via NSCs α2A-adrenoceptor.

Development and validation of a model for predicting in-hospital mortality in patients with sepsis-associated kidney injury receiving renal replacement therapy: a retrospective cohort study based on the MIMIC-IV database.

SAKI is a common and serious complication of sepsis, contributing significantly to high morbidity and mortality, especially in patients requiring RRT. Early identification of high-risk patients enables timely interventions and improvement in clinical outcomes. The objective of this study was to develop and validate a predictive model for in-hospital mortality in patients with SAKI receiving RRT. Patients with SAKI receiving RRT from the MIMIC-IV database were retrospectively enrolled and randomly assigned to either the training cohort or the testing cohort in a 7:3 ratio. LASSO regression and Boruta algorithm were utilized for feature selection. Subsequently, three machine learning models-CART, SVM and LR-were constructed, and their predictive efficacy was assessed using a comprehensive set of performance indicators. Feature importance analysis was performed to determine the contribution of each feature to a model's predictions. Finally, DCA was employed to evaluate the clinical utility of the prediction models. Additionally, a clinical nomogram was developed to facilitate the interpretation and visualization of the LR model. A total of 1663 adults were ultimately enrolled and randomly allocated into the training cohort (n = 1164) or the testing cohort (n = 499). Twenty-eight variables were evaluated for feature selection, with eight ultimately retained in the final model: age, MAP, RR, lactate, Cr, PT-INR, TBIL and CVP. The LR model demonstrated commendable performance, exhibiting robust discrimination in both the training cohort (AUROC: 0.73 (95% CI 0.70-0.76); AUPRC: 0.75 (95% CI 0.72-0.79); accuracy: 0.66 (95% CI 0.63-0.68)) and the testing cohort (AUROC: 0.72 (95% CI 0.68-0.76); AUPRC: 0.73 (95% CI 0.67-0.79); accuracy: 0.65 (95% CI 0.61-0.69)). Furthermore, there was good concordance between predicted and observed values in both the training cohort (χ2 = 4.41, p = 0.82) and the testing cohort (χ2 = 4.16, p = 0.84). The results of the DCA revealed that the LR model provided a greater net benefit compared to other prediction models. The LR model exhibited superior performance in predicting in-hospital mortality in patients with SAKI receiving RRT, suggesting its potential utility in identifying high-risk patients and guiding clinical decision-making.

The Influence of Regional Anesthesia on the Systemic Stress Response

Background: The systemic stress response to surgery is a complex physiological process characterized by neuroendocrine, sympathetic, and inflammatory activation. While necessary for survival, this response can lead to adverse outcomes such as hyperglycemia, immune suppression, cardiovascular complications, and delayed recovery. Regional anesthesia (RA) has been shown to modulate this stress response more effectively than general anesthesia (GA) by blocking nociceptive signaling and attenuating the release of stress mediators. Objectives: This review aims to elucidate how RA influences the systemic stress response, highlighting its clinical benefits in reducing postoperative pain, improving hemodynamic stability, minimizing inflammatory responses, and preserving immune function. Additionally, this review examines evidence from clinical trials supporting using RA to improve surgical outcomes, particularly in high-risk populations. Methods: A comprehensive narrative review of the literature was conducted to explore the physiological impact of RA on the systemic stress response and its associated clinical outcomes. Studies comparing RA to GA across various surgical procedures were evaluated, focusing on neuroendocrine modulation, sympathetic inhibition, inflammatory attenuation, and the implications for pain management, cardiovascular and pulmonary function, and immune preservation. Results: RA significantly attenuates the neuroendocrine response by reducing the release of cortisol and catecholamines, thereby improving hemodynamic stability and reducing myocardial oxygen consumption. RA also inhibits the sympathetic nervous system, leading to improved cardiovascular outcomes. Furthermore, RA mitigates the inflammatory response by reducing pro-inflammatory cytokine levels, reducing the risk of systemic inflammatory response syndrome (SIRS), sepsis, and pulmonary complications. Clinical studies and meta-analyses consistently demonstrate that RA reduces postoperative pain, opioid consumption, and the incidence of cardiovascular and pulmonary complications, particularly in elderly and high-risk patients. Conclusions: RA offers a significant advantage in modulating the systemic stress response to surgery, improving postoperative outcomes by reducing pain, enhancing cardiovascular stability, and preserving immune function. Its benefits are particularly pronounced in high-risk populations such as the elderly or those with pre-existing comorbidities. Given the growing evidence supporting its efficacy, RA should be considered a critical component of multimodal perioperative care strategies aimed at minimizing the systemic stress response and improving recovery. Future research should optimize RA techniques and identify patient-specific factors to enhance therapeutic benefits.

Regulation of mitochondrial autophagy by lncRNA MALAT1 in sepsis-induced myocardial injury

BackgroundSepsis-induced myocardial injury (SIMI) is a severe complication of sepsis, contributing significantly to mortality. Mitochondrial dysfunction and dysregulated autophagy are implicated in SIMI pathogenesis. Long non-coding RNA MALAT1 has been associated with various diseases, including sepsis, but its role in SIMI remains unclear.ObjectiveThis study aimed to investigate the role of lncRNA MALAT1 in SIMI, specifically in the regulation of mitochondrial autophagy.MethodsA sepsis-induced cardiomyopathy model was established in mice, and the cardiac tissues were analyzed. The expression of lncRNA MALAT1 was modulated and its effects on mitochondrial autophagy, myocardial injury, inflammation, and apoptosis were assessed. Furthermore, the interaction between MALAT1 and miR-146a was explored, as well as the involvement of the TLR4/NF-kB/MAPK signaling pathway.ResultsActivation of mitochondrial autophagy by urolithin A (UA) alleviated SIMI, inflammation, and cardiac dysfunction. Downregulation of MALAT1 enhanced mitochondrial autophagy, stabilized the mitochondrial membrane potential, and inhibited mitochondrial reactive oxygen species (ROS) production, leading to improved cell viability and reduced myocardial injury. Furthermore, MALAT1 interacted with miR-146a, and their modulation influenced mitochondrial autophagy, myocardial injury, and inflammation. The TLR4/NF-kB/MAPK signaling pathway was implicated in these processes.ConclusionOur findings suggest that lncRNA MALAT1 plays a crucial role in SIMI by modulating miR-146a-mediated mitochondrial autophagy and the TLR4/NF-kB/MAPK signaling pathway. These results provide new insights into the pathogenesis of SIMI and potential therapeutic targets.

Reduced glutathione attenuates pediatric sepsis-associated encephalopathy by inhibiting inflammatory cytokine release and mitigating lipid peroxidation-induced brain injury.

Sepsis-associated encephalopathy (SAE) is a severe complication of sepsis. Reduced glutathione (GSH) has antioxidant properties and is used as a neuroprotective agent in some studies. However, research on the application of exogenous GSH in the treatment of SAE is limited. This study aimed to determine the effects of exogenous GSH in pediatric SAE patients and mice. We evaluated clinical parameters, inflammatory factors, and oxidative stress before and after GSH treatment. The clinical trials demonstrated that GSH treatment improved brain damage markers (S-100 beta protein, brain fatty acid-binding protein), increased neurological status scores (Glasgow coma scale), and reduced Pediatric Risk of Mortality III scores in children with SAE. GSH treatment also significantly reduced the levels of inflammatory factors (interleukin-6, tumor necrosis factor-α) and decreased lipid peroxidation (superoxide dismutase). Additionally, GSH reduced lipid peroxidation resulting from abnormal lipid metabolism, as indicated by the levels of acyl-CoA synthetase long-chain family member 4, lysophosphatidylcholine acyltransferase 3, and glutathione peroxidase 4. In-vivo experiments showed that the neuroprotective effect of GSH was dose-dependent, with better effects observed at medium and high doses. Furthermore, GSH alleviated brain damage, suppressed the release of inflammatory factors, and inhibited lipid peroxidation in SAE mice. The animal experiments also showed that GSH reduces lipid peroxidation through the 15-lipoxygenase/phosphatidylethanolamine binding protein 1/glutathione peroxidase 4 pathway. Our study suggests that exogenous GSH has neuroprotective effects in pediatric SAE. These findings provide a basis for the potential use of GSH as a therapeutic method for SAE.

Screening of hub genes for sepsis-induced myopathy by weighted gene co-expression network analysis and protein-protein interaction network construction

Sepsis-induced myopathy is one of the serious complications of sepsis, which severely affects the respiratory and peripheral motor systems of patients, reduces their quality of life, and jeopardizes their lives, as evidenced by muscle atrophy, loss of strength, and impaired regeneration after injury. The pathogenesis of sepsis-induced myopathy is complex, mainly including cytokine action, enhances free radical production in muscle, increases muscle protein hydrolysis, and decreases skeletal muscle protein synthesis, etc. The above mechanisms have been demonstrated in existing studies. However, it is still unclear how the overall pattern of gene co-expression affects the pathological process of sepsis-induced myopathy. Therefore, we intend to identify hub genes and signaling pathways. Weighted gene co-expression network analysis was our main approach to study gene expression profiles: skeletal muscle transcriptome in ICU patients with sepsis-induced multi-organ failure (GSE13205). After data pre-processing, about 15,181 genes were used to identify 13 co-expression modules. Then, 16 genes (FEM1B, KLHDC3, GPX3, NIFK, GNL2, EBNA1BP2, PES1, FBP2, PFKP, BYSL, HEATR1, WDR75, TBL3, and WDR43) were selected as the hub genes including 3 up-regulated genes and 13 down-regulated genes. Then, Gene Set Enrichment Analysis was performed to show that the hub genes were closely associated with skeletal muscle dysfunction, necrotic and apoptotic skeletal myoblasts, and apoptosis in sepsis-induced myopathy. Overall, 16 candidate biomarkers were certified as reliable features for more in-depth exploration of sepsis-induced myopathy in basic and clinical studies.

Perioperative Antibiotic Use in Pediatric Solid Tumor Resection: A Two-center Retrospective Cohort Study

PurposeThere is no consensus on the perioperative use of antibiotics in pediatric solid tumor resection. This study collected data from two pediatric centers that utilize perioperative antibiotics to varying degrees in pediatric solid tumor patients to investigate the occurrence of postoperative sepsis and infectious complications. MethodsA two-institution, retrospective cohort study was performed. Charts of children who underwent solid tumor resection between July 2018–June 2021 were reviewed. Patient characteristics, diagnosis, operative data, perioperative antibiotic use, and postoperative infection/sepsis were analyzed within 30 days of surgery. The primary outcome was surgical site infection (SSI) or systemic sepsis within 30 days of surgery. Fisher's tests were performed to evaluate differences. Results250 patients underwent tumor resection between July 2018 and June 2021 at both centers. The median age was 4 years [Range: 0.02–26.1]. Seventy-five percent (N = 188) received perioperative antibiotics prophylaxis (AP), while 25 % of patients did not receive AP (N = 62). Only one patient in the AP group (0.5 %) developed postoperative sepsis, while 12 patients (19.4 %) in the non-AP group developed sepsis (p < 0.0001). There were 3 SSI in the AP group and none in the non-AP group (p = 1.0). ConclusionsThe administration of AP in children undergoing solid tumor resection is associated with a reduced rate of postoperative sepsis but no difference in SSI. This could possibly be related to bacterial translocation during surgery and the seeding of indwelling central venous access catheters. Our results support the standardized use of AP in this population. Type of StudyRetrospective Cohort Study. Level of EvidenceIII.

Ccl5+ Macrophages drive pro-inflammatory responses and neutrophil recruitment in sepsis-associated acute kidney injury

Sepsis leads to dysfunctional immune responses with multi-organ damage, and acute kidney injury (AKI) is a common complication of sepsis. To gain a deeper understanding of the specific underlying mechanisms of sepsis, we investigated the effects of specific macrophages on sepsis. To gain a deeper understanding of the specific underlying mechanisms of sepsis, we investigated the effects of specific macrophages on sepsis. Single-cell sequencing of a mouse model of endotoxemia revealed that sepsis is a common complication of sepsis. Single-cell sequencing of a mouse model of endotoxemia revealed that the emerging macrophage subpopulation Ccl5+ Mac was significantly pro-inflammatory, activating a large number of pathways activating a large number of pathways associated with immune response and inflammatory response, including IL6-JAK-STAT3 signaling, TGF-β signaling, and inflammatory response. Interestingly, we found that Ccl5+ Mac recruits neutrophil through CCL5-CCR1 ligand receptor pairs by cellular communication analysis thereby further affecting sepsis. We therefore hypothesize that this macrophage subpopulation is actively involved in the underlying molecular mechanisms of AKI. We therefore hypothesize that this macrophage subpopulation is actively involved in the underlying molecular mechanisms of AKI in sepsis and provide valuable insights.

Fluid resuscitation and application of vasoactive drugs in septic shock: timing, evaluation criteria, and specifications

Septic shock (SS), the most severe complication of sepsis, has always been a major challenge and research focus in the field of critical care treatment. SS is categorized as a distributive shock, where fluid resuscitation and the use of vasoactive drugs are the two standard measures for the clinical management of SS. However, it remains unclear how to accurately monitor macro-circulation, micro-circulation, and cellular metabolism indicators during the process of resuscitation, optimization, stabilization, and evacuation based on the dynamic pathophysiological processes of SS. This monitoring is essential to guide the comprehensive, individualized, and dynamic application of these two measures. Based on recent international management guidelines and literature review, the authors will propose relevant recommendations regarding the use of fluid therapy and vasoactive drugs.

Biomimetic Nanomodulator Regulates Oxidative and Inflammatory Stresses to Treat Sepsis-Associated Encephalopathy.

Sepsis-associated encephalopathy (SAE) is a devastating complication of sepsis, affecting approximately 70% of patients with sepsis in intensive care units (ICU). Although the pathophysiological mechanisms remain elusive, sepsis is typically accompanied by systemic inflammatory response syndrome (SIRS) and hyper-oxidative conditions. Here, we introduce a biomimetic nanomodulator (mAOI NP) that specifically targets inflammation site and simultaneously regulates oxidative and inflammatory stresses. mAOI NPs are constructed using metal-coordinated polyphenolic antioxidants (tannic acid) and flavonoid quercetin, which are then coated with macrophage membrane to enhance pharmacokinetics and enable SAE targeting. In a cecal ligation and puncture (CLP)-induced severe sepsis model, mAOI NPs effectively mitigate oxidative stress by purging reactive oxygen species, repairing mitochondrial damage and activating the Nrf2/HO-1 signaling pathway; while polarizing M1 macrophages or microglia toward anti-inflammatory M2 subtype. mAOI NPs potently inhibit sepsis progress, prolong overall survival from 25 to 66% and enhance learning and memory capabilities in SAE mice. Further proteomics analysis reveals that mAOI NPs modulate neurodevelopment processes related to learning and memory formation while also exerting anti-inflammatory and antioxidative effects on brain tissue responses associated with SAE pathology. This study offers significant potential for improving patient outcomes and revolutionizing the treatment landscape for this devastating complication of sepsis.

Effect of mitochondrial translocator protein TSPO on LPS-induced cardiac dysfunction

IntroductionSepsis-induced cardiac dysfunction is one of the most serious complications of sepsis. The mitochondrial translocator protein (TSPO), a mitochondrial outer membrane protein, is widely used as a diagnostic marker of inflammation-related diseases and can also lead to the release of inflammatory components. However, whether TSPO has a therapeutic effect on sepsis-induced cardiac dysfunction is unclear. ObjectivesThe aim of this study is to investigate the involvement of TSPO in the pathogenesis of sepsis-induced cardiac dysfunction and elucidate its underlying mechanism, as well as develop therapeutic strategies targeting TSPO for the prevention and treatment of sepsis-induced cardiac dysfunction. MethodsThe sepsis-induced cardiac dysfunction model was established by intraperitoneal injection of lipopolysaccharide (LPS) in C57BL/6 mice (LPS-induced cardiac dysfunction, LICD). TSPO knockout mice were constructed,and the effects of TSPO was detected by survival rate, echocardiography, HE staining, mitochondrial electron microscopy, TUNEL staining. TSPO-binding proteins were identified by co-immunoprecipitation and mass spectrometry. The mechanisms underlying between TSPO and voltage-dependent anion channel (VDAC) was studied through western blot and immunofluorescence. Proteolysis-Targeting Chimeras (PROTAC) technology was used to construct TSPO-PROTAC molecules that can degrade TSPO. ResultsOur present study found that LPS increased cardiac TSPO expression. Knockout of TSPO in C57BL/6 mice with LICD attenuated the cardiac pathology, mitochondrial dysfunction, and apoptosis of cardiomyocytes and significantly improved cardiac function and survival rate. Co-immunoprecipitation and mass spectrometry identified VDAC as a TSPO binding protein.Down-regulation of TSPO reduced PKA-mediated VDAC phosphorylation and VDAC oligomerization, ameliorated mitochondrial function, and reduced cardiomyocyte apoptosis. The study has clinical translational potential, because administration of TSPO-PROTAC to degrade TSPO improved cardiac function in mice with LICD. ConclusionThis study elucidated the effect of TSPO in LICD, providing a new therapeutic strategy to down-regulate TSPO by administration of TSPO-PROTAC for the prevention and treatment of LICD.