Development Of Sepsis Research Articles

Gut microbiota, circulating inflammatory proteins and sepsis: a bi-directional Mendelian randomization study.

Gut microbiota is closely related to the occurrence and development of sepsis. However, the causal effects between the gut microbiota and sepsis, and whether circulating inflammatory proteins act as mediators, remain unclear. Gut microbiota, circulating inflammatory proteins, and four sepsis-related outcomes were identified from large-scale genome wide association studies (GWAS) summary data. Inverse Variance Weighted (IVW) was the primary statistical method. Additionally, we investigated whether circulating inflammatory proteins play a mediating role in the pathway from gut microbiota to the four sepsis-related outcomes. There were 14 positive and 15 negative causal effects between genetic liability in the gut microbiota and four sepsis-related outcomes. Additionally, eight positive and four negative causal effects were observed between circulating inflammatory proteins and the four sepsis-related outcomes. Circulating inflammatory proteins do not act as mediators. Gut microbiota and circulating inflammatory proteins were causally associated with the four sepsis-related outcomes. However, circulating inflammatory proteins did not appear to mediate the pathway from gut microbiota to the four sepsis-related outcomes.

Prognostication of the development of septic complications in children with burn injuries.

Aim: To determine the prognostic criteria for the development of septic complications in children with thermal injury. Materials and Methods: A single-center retrospective-prospective cohort study included a retrospective analysis of 98 medical histories of children of different ages with severe burns who were treated from 2007 to 2017. A prospective study was conducted among children (n=63) from 1 to 5 years old, who received various degrees severity burn injury, according to an open comparative method in the period from 2018 to 2021. Results: Indicators of a high risk of developing sepsis were burns by flames of any etiology, damage severity index ≥75 units, total burn surface ≥25 %, deep burn area ≥ 5%. The threshold value of procalcitonin (PCT) ≥ 0.86 ng/ml on the 1st-3rd day and PCT > 0.51 ng/ml on the 7th day of burn disease, had a prognostic value for assessing the probability of sepsis. On the 1st day of hospitalization, the development of sepsis was predicted if the C-reactive protein (CRP) value was higher than 6.98 ng/ml, on the 3rd - the CRP level was above 7.43 ng/ml, on the 7th day - above 7.28 ng/ml. Conclusions: Based on the obtained data, we selected the criteria with the best prognostic characteristics, which allows us to predict and prevent the development of sepsis in the early stages of burn disease in children.

Прогнозирование летального исхода у госпитальных пациентов с COVID-19 и коморбидной патологией

Aim. To identify predictors of fatal outcome of COVID-19 in comorbid patients hospitalized in a specialized сovid-hospital in Nizhny Novgorod. Design. A single-center retrospective study. Material and methods. The data of 284 patients admitted to the specialized covid hospital in Nizhny Novgorod were analyzed. Three study groups were identified: the main group (n = 207) included people with new coronavirus infection (NCI) who had cardiovascular (CVD) and comorbid diseases, the comparison group consisted of patients with NCI and CVD without a burdened comorbid background (n = 24), the control group included the remaining patients with NCIS without CVD and comorbid pathology (n = 53). A comprehensive analysis of clinical and demographic, laboratory, instrumental indicators, the structure of comorbid pathology, as well as therapeutic approaches was Performed. Results. The assessment of the occurrence of CVD showed that hypertension was diagnosed in the majority of hospitalized patients — 226 (79.6%) persons, about half of the studied (146 (51.4%) people) had coronary heart disease, in 148 (52.1%) cases there was chronic heart failure, atrial fibrillation of various forms was in every fifth patient — in 59 (20.8%) cases. The analysis of the comorbid status among the main group (n = 207) demonstrated the widespread occurrence of chronic kidney disease (CKD) of various stages, which was recorded in 192 (92.7%) patients, and type 2 diabetes in 76 (36.7%) patients. The peculiarities of the course of COVID-19 among patients on hemodialysis were established: they had a tendency to hypercoagulation, estimated by the level of D-dimer (p = 0.045), sepsis developed more often, respiratory failure progressed more rapidly, requiring artificial lung ventilation (p = 0.011). Among people with CKD C5, mortality was also statistically significantly higher than in patients with other stages of CKD (p = 0.048). A mathematical model was developed to determine the risk of death among hospitalized patients with NCI. According to this model, the risk of death increased with the development of acute myocardial infarction, newly diagnosed atrial fibrillation, sepsis, decreased saturation, with increasing age of patients, with a decrease in the level of C-reactive protein (CRP), and an increase in D-dimer. Taking favipiravir, tocilizumab and statins reduced the risk of death. Conclusion. The most common cardiovascular pathology in patients hospitalized for NCI was hypertension, and atrial fibrillation prevailed among cardiac arrhythmias. It was noted that CKD prevails in the structure of comorbid pathologies. In people with severe NCI, who have CVD and CKD C5, a greater predisposition to the development of sepsis and an increase in respiratory failure was estamblished, which was the cause of progressive deterioration of the condition and subsequently led to death. In addition, we have shown that the probability of death in patients with CVD and COVID-19 was influenced by the older age of the patient, a decrease in saturation, a decrease in CRP, and an increase in D-dimer. As a drug therapy, the most beneficial effect on survival was the administration of favipiravir, tocilizumab and statins. Keywords: COVID-19, comorbidity, cardiovascular diseases, mortality, hemodialysis

Evaluation of d-dimer as outcome biomarker in COVID-19 acute respiratory distress patients.

Acute respiratory distress syndrome is a significant complication in critical care patients. COVID-19 (C19)-associated severe respiratory failure is related to it, and d-dimer rise predicts a worse outcome. To investigate the association between d-dimer and the severity of this respiratory syndrome, we conducted a study in C19 intubated patients. A retrospective, single-center observational study was conducted with 64 C19 adult intubated patients. Strata of d-dimer results between patients was evaluated using survival analysis. Survival was higher in mild respiratory distress patients. D-dimer showed poor sensitivity and specificity in predicting respiratory failure severity. Risk assessment for death showed a higher prevalence of admission d-dimer results (HR 1.335; 95% CI 0.695-2.564). Our sample confidently represented the medical profile of C19 severe patients. Sepsis development in C19 is associated with the inflammatory storm in respiratory distress syndrome. As the receiver operating curves show, the increase in d-dimer results is consistent with inflammation rather than a prognostic biomarker. As expected, severe respiratory distress patients presented higher mortality. In summary, d-dimer results are not associated with the prognosis of C19 respiratory distress syndrome patients.

Polymorphisms in Glutathione S-transferase genes, Development, and Progression of Sepsis

Polymorphisms in Glutathione S-transferase genes, Development, and Progression of Sepsis

Toll-like receptor 4 damages the intestinal epithelial cells by activating endoplasmic reticulum stress in septic rats.

The severity of acute gastrointestinal injury (AGI) is a critical determinant of survival in sepsis. However, there is no specifically interventional management for gastrointestinal dysfunction. Toll-like Receptor 4 (TLR4) is an important contributor to sepsis-induced multiple organ dysfunction syndrome. So, we investigated the effect of TLR4 on leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) + cells and goblet cells and its potential mechanism. A cecal ligation and puncture (CLP) model reflecting the development of clinical sepsis was developed. Tak-242, a TLR4 inhibitor, was administered to septic rats at a dose of 3 mg/kg via intraperitoneal injection. Immunohistochemistry was performed to detect TLR4 and Lgr5+ cells. AB-PAS staining was performed to detect goblet cells. MUC1 and MUC2 secreted by goblet cells, biomarkers of endoplasmic reticulum (ER) stress and inflammatory cytokines in the intestine were detected by western blotting and real-time PCR. We found that the upregulation of the TLR4/NF-κB signaling pathway activated intestinal inflammatory response in sepsis. Meanwhile, the structure of intestinal mucosa was destroyed, Lgr5+ cells and goblet cells count were significantly reduced, and the secretory function of goblet cells also decreased. Further studies have found that TLR4 increased the levels of activating transcription factor-6 (ATF6), XBP1, ER chaperone (Bip) and CHOP, but did not activate the protein kinase RNA (PKR)-like ER kinase (P-PERK). We concluded that the inhibition of TLR4/NF-κB signaling pathway can reduce intestinal inflammatory response, protect intestinal mucosa, protect Lgr5+ cells, goblet cells and relieve ER stress. Our findings suggest that Tak-242 protects Lgr5+ cells and goblet cells after sepsis, partly may be through the suppression of ER stress. Thus, inhibition of TLR4-mediated ER stress may be a promising therapy of septic AGI.

Aetiology, Risk factors, and Outcome of Central Line-associated Bloodstream Infections in Respiratory ICU Patients at a Tertiary Care Centre, Cuttack, Odisha, India: A Prospective Cohort Study

Introduction: Central Venous Catheters (CVCs) are used for monitoring and managing critically-ill patients. However, their use can lead to serious infectious complications, resulting in significant morbidity, additional medical costs and mortality. Aim: To analyse the causative pathogens and the associated risk factors involved in the causation of central line-related infections and their outcomes. Materials and Methods: This prospective cohort study was conducted among 66 patients admitted to the 10-bed Respiratory Intensive Care Unit (RICU) at the Department of Pulmonary Medicine, SCB Medical College and Hospital, a tertiary-care teaching hospital in Cuttack, Odisha, India, from March 2021 to October 2022, who required central line placement for 48 hours or more. These patients were followed daily and upon the development of new-onset sepsis after 48 hours, two blood samples were collected from both central and peripheral sites for culture and antibiotic susceptibility testing, after excluding other sources of infections. Results: The mean age of patients with CLABSI was 62.85±14.95 years, with the most commonly affected age group being 55-74 years. Total of 66 patients had CVCs in place for more than 48 hours, resulting in 664 catheter days. The overall rate of Central Line Associated Bloodstream Infection (CLABSI) was 30.12 per 1,000 catheter days. The risk factors significantly associated with the development of CLABSI were diabetes mellitus, duration of hospitalisation, APACHE score, length of ICU stay and days of catheter in-situ. However, multivariate analysis revealed that only the length of Intensive Care Unit (ICU) stay (p=0.003) and the presence of diabetes (p=0.012) were independent predictors of acquiring CLABSI. The most common pathogens isolated were Acinetobacter (30%), followed by Enterococcus (25%), Staphylococcus aureus (20%), Methicillin-resistant Staphylococcus Aureus (MRSA) (10%), Pseudomonas (10%) and Coagulase-Negative Staphylococcus (CoNS) (5%). All Gram-positive and Gram-negative pathogens showed 100% sensitivity to linezolid, teicoplanin, vancomycin and polymyxin B, as well as tigecycline, respectively. The remaining strains were Multidrug Resistant (MDR). The overall mortality rate was 66.7%, with CLABSI-associated mortality at 60%. Conclusion: The incidence of CLABSI was high, with significant risk factors significantly associated were prolonged duration of catheterisation, length of hospital and ICU stays, Acute Physiology and Chronic Health Evaluation (APACHE) II score and diabetes mellitus. Gram-positive bacteria predominated, followed by Gram-negative bacteria, with a significant proportion of MDR organisms.

Cathelicidin-HG Alleviates Sepsis-Induced Platelet Dysfunction by Inhibiting GPVI-Mediated Platelet Activation.

Platelet activation contributes to sepsis development, leading to microthrombosis and increased inflammation, which results in disseminated intravascular coagulation and multiple organ dysfunction. Although Cathelicidin can alleviate sepsis, its role in sepsis regulation remains largely unexplored. In this study, we identified Cath-HG, a novel Cathelicidin from Hylarana guentheri skin, and analyzed its structure using nuclear magnetic resonance spectroscopy. The modulatory effect of Cath-HG on the symptoms of mice with sepsis induced by cecal ligation and puncture was evaluated invivo, and the platelet count, degree of organ damage, and microthrombosis were measured. The antiplatelet aggregation activity of Cath-HG was studied invitro, and its target was verified. Finally, we further investigated whether Cath-HG could regulate thrombosis invivo in a FeCl3 injury-induced carotid artery model. The results showed that Cath-HG exhibited an α-helical structure in sodium dodecyl sulfate solution and effectively reduced organ inflammation and damage, improving survival in septic mice. It alleviated sepsis-induced thrombocytopenia and microthrombosis. Invitro, Cath-HG specifically inhibited collagen-induced platelet aggregation and modulated glycoprotein VI (GPVI) signaling pathways. Dot blotting, enzyme-linked immunosorbent assay, and pull-down experiments confirmed GPVI as the target of Cath-HG. Molecular docking and amino acid residue truncations/mutations identified crucial sites of Cath-HG. These findings suggest that GPVI represents a promising therapeutic target for sepsis, and Cath-HG may serve as a potential treatment for sepsis-related thrombocytopenia and thrombotic events. Additionally, identifying Cath-HG as a GPVI inhibitor provides insights for developing novel antithrombotic therapies targeting platelet activation mediated by GPVI.

SP1-stimulated miR-208a-5p aggravates sepsis-induced myocardial injury via targeting XIAP

The development of sepsis can lead to many organ dysfunction and even death. Myocardial injury is one of the serious complications of sepsis leading to death. New evidence suggests that microRNAs (miRNAs) play a critical role in infection myocardial injury. However, the mechanism which miR-208a-5p regulates sepsis-induced myocardial injury remains unclear. To mimic sepsis-induced myocardial injury in vitro, rat primary cardiomyocytes were treated with LPS. Cell viability and apoptosis were tested by CCK-8 and flow cytometry, respectively. The secretion of inflammatory factors was analyzed by ELISA. mRNA and protein levels were detected by RT-qPCR and Western blotting. The interaction among SP1, XIAP and miR-208a-5p was detected using dual luciferase report assay. Ultrasonic analysis and HE staining was performed to observe the effect of miR-208a-5p in sepsis-induced rats. Our findings indicated that miR-208a-5p expression in primary rat cardiomyocytes was increased by LPS. MiR-208a-5p inhibitor reversed LPS-induced cardiomyocytes injury through inhibiting the apoptosis. Furthermore, the inflammatory injury in cardiomyocytes was induced by LPS, which was rescued by miR-208a-5p inhibitor. In addition, downregulation of miR-208a-5p improved LPS-induced sepsis myocardial injury in vivo. Mechanistically, XIAP might be a target gene of miR-208a-5p. SP1 promoted transcription of miR-208a by binding to the miR-208a promoter region. Moreover, silencing of XIAP reversed the regulatory of miR-208a-5p inhibitor on cardiomyocytes injury. To sum up, those findings revealed silencing of miR-208a-5p could alleviate sepsis-induced myocardial injury, which would grant a new process for the treatment of sepsis.

Ghrelin/GHSR Axis Induced M2 Macrophage and Alleviated Intestinal Barrier Dysfunction in a Sepsis Rat Model by Inactivating E2F1/NF-κB Signaling.

Sepsis is an inflammatory reaction disorder state that is induced by infection. The activation and regulation of the immune system play an essential role in the development of sepsis. Our previous studies have shown that ghrelin ameliorates intestinal dysfunction in sepsis. Very little is known about the mechanism of ghrelin and its receptor (GHSR) on the intestinal barrier and the immune function of macrophage regulation. Our research is to investigate the regulatory effect and molecular mechanism of the ghrelin/GHSR axis on intestinal dysfunction and macrophage polarization in septic rats. A rat model of sepsis was established by cecal ligation and puncture (CLP) operation. Then, the sepsis rats were treated with a ghrelin receptor agonist (TZP-101) or ghrelin inhibitor (obestatin). The results suggested that TZP-101 further enhanced ghrelin and GHSR expressions in the colon and spleen of septic rats and obestatin showed the opposite results. Ghrelin/GHSR axis ameliorated colonic structural destruction and intestinal epithelial tight junction injury in septic rats. In addition, the ghrelin/GHSR axis promoted M2-type polarization of macrophages, which was characterized by the decreases of IL-1β, IL-6, and TNF-α, as well as the increase of IL-10. Mechanistically, the ghrelin/GHSR axis promoted E2F2 expression and suppressed the activation of the NF-κB signaling pathway in septic rats. Collectively, targeting ghrelin/GHSR during sepsis may represent a novel therapeutic approach for the treatment of intestinal barrier injury.

Hematological and Biochemical Parameters of Macropod Progressive Periodontal Disease in Wild Western Gray Kangaroos

Macropod progressive periodontal disease (MPPD), known as Lumpy Jaw, poses a persistent and potentially fatal threat in Western gray kangaroos when they are kept in captivity. Such a condition leads to the development of osteomyelitis and sepsis in Western gray kangaroos (Macropus fuliginosus). This case study presented the inaugural examination of hematological and biochemical aspects of MPPD with a progression toward sepsis in a captive environment. The primary objective of this research was to pinpoint hematological and biochemical indicators associated with severe MPPD in a Western gray kangaroo held in captivity. The study employed various methods, including clinical, radiographical, hematological, and biochemical analyses, as well as microbiological study methods. The case was a 2.5-year-old male wild Western gray kangaroo with fever (39.7 °C), dehydration, dyspnea, tachycardia, and involuntary jaw clenching due to stress and agitation. The kangaroo had a history of lethargy, anorexia, swelling of the soft tissues of the lower jaw on the left side, and tenderness during palpation. A radiograph of the head revealed mandible proliferative lesions. The hematological and biochemical examinations indicated an increase in the total count of leucocytes, level of neutrophils, number of erythrocytes, hematocrit level, and lymphopenia. Increased activity of alkaline phosphatase, amylase, and creatinine elevated azotemia. There was a decrease in the content of albumin, glucose, and total bilirubin. The bacteria, consisting of Fusobacteriaceae spp., Porphyromonadaceae spp., and Bacteroidaceae spp., were found and identified in all samples. However, this comprehensive diagnosis of MPPD based on clinical signs, radiography, and especially hematological and biochemical parameters of the septic process can be helpful in diagnosis and treatment.

Pneumonia in the first week after polytrauma is associated with reduced blood levels of soluble herpes virus entry mediator.

Pneumonia develops frequently after major surgery and polytrauma and thus in the presence of systemic inflammatory response syndrome (SIRS) and organ dysfunction. Immune checkpoints balance self-tolerance and immune activation. Altered checkpoint blood levels were reported for sepsis. We analyzed associations of pneumonia incidence in the presence of SIRS during the first week of critical illness and trends in checkpoint blood levels. Patients were studied from day two to six after admission to a surgical intensive care unit (ICU). Blood was sampled and physician experts retrospectively adjudicated upon the presence of SIRS and Sepsis-1/2 every eight hours. We measured the daily levels of immune checkpoints and inflammatory markers by bead arrays for polytrauma patients developing pneumonia. Immune checkpoint time series were additionally determined for clinically highly similar polytrauma controls remaining infection-free during follow-up. We performed cluster analyses. Immune checkpoint time trends in cases and controls were compared with hierarchical linear models. For patients with surgical trauma and with and without sepsis, selected immune checkpoints were determined in study baseline samples. In polytrauma patients with post-injury pneumonia, eleven immune checkpoints dominated subcluster 3 that separated subclusters 1 and 2 of myeloid markers from subcluster 4 of endothelial activation, tissue inflammation, and adaptive immunity markers. Immune checkpoint blood levels were more stable in polytrauma cases than controls, where they trended towards an increase in subcluster A and a decrease in subcluster B. Herpes virus entry mediator (HVEM) levels (subcluster A) were lower in cases throughout. In unselected surgical patients, sepsis was not associated with altered HVEM levels at the study baseline. Pneumonia development after polytrauma until ICU-day six was associated with decreased blood levels of HVEM. HVEM signaling may reduce pneumonia risk by strengthening myeloid antimicrobial defense and dampening lymphoid-mediated tissue damage. Future investigations into the role of HVEM in pneumonia and sepsis development and as a predictive biomarker should consider the etiology of critical illness and the site of infection.

Definition, epidemiology and characterization of sepsis

Sepsis is a condition that occurs when the body's response to infection becomes unbalanced and potentially life-threatening. In this study, there is a focus on understanding and addressing sepsis. This detailed review explores how sepsis is defined in its prevalence in populations and how it is present clinically. The development of sepsis involves a series of events triggered by infections resulting in inflammation and dysfunction in organs. The symptoms of sepsis can range from signs like fever and changes in state to more severe complications such as septic shock. Early recognition of these symptoms using criteria like Systemic inflammatory response syndrome (SIRS) is crucial for intervention, which can greatly impact patient outcomes. Various diagnostic markers, imaging techniques and a deeper understanding of the pathophysiology behind sepsis have contributed to identification and targeted treatment approaches. Managing sepsis involves a combination of therapy, support for blood circulation, respiratory interventions and careful use of agents that modulate the system. It's important to emphasize the efforts among healthcare professionals from disciplines when it comes to managing sepsis effectively. Providing follow up care is essential for survivors as they may experience long term consequences such as sepsis syndrome. Due to its impact on health ongoing research is necessary to explore therapeutic options and refine existing strategies for managing sepsis effectively. The field continues to evolve with advancements, in precision medicine host directed therapies and interdisciplinary collaboration playing roles. This review seeks to grasp the concept of sepsis, providing insights into its various aspects, including the difficulties, in diagnosis and the ever-evolving treatment strategies.

Gallic Acid Protects from Sepsis-Induced Acute Lung Injury.

Sepsis, a leading global cause of morbidity and mortality, involves multiple organ dysfunction syndromes driven by free radical-mediated processes. Uncontrolled inflammation in early sepsis stages can lead to acute lung injury (ALI). Activated leukocytes generate reactive oxygen species, contributing to sepsis development. Gallic acid, a phenolic compound, is known for its antimicrobial properties. This study aims to observe gallic acid's protective and restorative effect on the lungs in an experimental sepsis model. Male Wistar albino rats were subjected to a feces intraperitoneal injection procedure (FIP) to induce sepsis. Four groups were formed: normal control, FIP alone, FIP with saline, and FIP with gallic acid. Gallic acid was administered intraperitoneally at 20 mg/kg/day. Blood samples were collected for biochemical analysis, and computed tomography assessed lung tissue histopathologically and radiologically. Gallic acid significantly decreased malondialdehyde, IL-6, IL-1β, TNF-α, CRP levels, oxidative stress, and inflammation indicators. Lactic acid levels decreased, suggesting improved tissue oxygenation. Histopathological examinations revealed reduced lung damage in the gallic-acid-treated group. Computed tomography confirmed lower lung density, indicating less severe inflammation. Arterial blood gas analysis demonstrated improved oxygenation in gallic-acid-treated rats. Gallic acid exhibited anti-inflammatory and antioxidant effects, reducing markers of systemic inflammation and oxidative stress. The findings support its potential to protect against ALI during sepsis. Comparable studies underline gallic acid's anti-inflammatory properties in different tissues. Early administration of gallic acid in sepsis models demonstrated protective effects against ALI, emphasizing its potential as an adjunct therapy to mitigate adverse outcomes. The study proposes gallic acid to reduce mortality rates and decrease the need for mechanical ventilation during sepsis-induced ALI.

CD4 + T cells ferroptosis is associated with the development of sepsis in severe polytrauma patients

BackgroundImmunological disorder remains a great challenge in severe poly-trauma, in which lymphopenia is an important contributor. The purpose of present study is to explore whether ferroptosis, a new manner of programmed cell death (PCD), is involved in the lymphocyte depletion and predictive to the adverse prognosis of severe injuries. Patients and MethodsSevere polytrauma patients admitted from January 2022 to December 2022 in our trauma center were prospectively investigated. Peripheral blood samples were collected at admission (day 1), day 3 and day 7 from them. Included patients were classified based on whether they developed sepsis or not. Clinical outcomes, systematic inflammatory response, lymphocyte subpopulation, CD4 + T cell ferroptosis were collected, detected and analyzed. ResultsNotable lymphopenia was observed on the first day after severe trauma and failed to normalize on the 7th day if patients were complicated with sepsis, in which CD4 + T cell was the subset of lymphocyte that depleted most pronouncedly. Lymphocyte loss was significantly correlated with the acute and biphasic systemic inflammatory response. Ferroptosis participated in the death of CD4 + T cells, potentially mediated by the downregulation of xCT-GSH-GPX4 pathway. CD4 + T cells ferroptosis had a conducive predicting value for the development of sepsis following severe trauma. ConclusionsCD4 + T cells ferroptosis occurs early in the acute stage of severe polytrauma, which may become a promising biomarker and therapeutic target for post-traumatic sepsis.

Features of the respiratory burst state of neutrophils and the activity of NAD(P)-dependent dehydrogenases in patients with widespread purulent peritonitis in the prognosis of the development of sepsis

Aim: Studying of the respiratory burst state and NAD(P)-dependent dehydrogenases activities in blood neutrophils features in the forecast of the development of abdominal sepsis in patients with widespread purulent peritonitis (WPP).
 Materials and methods. The study involved 50 patients with WPP in the preoperative period. Abdominal sepsis was developed by 35 patients (70.0%) from 5 to 10 days postoperative period, 15 patients (30.0%) hadn’t complications. The respiratory burst condition of blood neutrophils was examined using a chemiluminescent assay. Intracellular activity of the NAD- and NADP-dependent dehydrogenases was researched with using bioluminescent methods.
 Results. It was found that patients with WPP whose dynamics of the preoperative period will develop sepsis the chemiluminescent activity of blood neutrophils was characterized by a reduced level of spontaneous synthesis of the primary reactive oxygen species (ROS) and elevated levels of spontaneous synthesis of secondary ROS relative of the indicators identified in patients without subsequent complications. The feature of neutrophil metabolism in WPP patients without subsequent development of sepsis was high activity of the anaerobic lactate dehydrogenase reaction and decrease in activity of the NADP-dependent decarboxylating malate dehydrogenase. In patients with WPP and the subsequent development of sepsis was found high level of NAD-dependent substrates outflow citric acid cycle in the reaction of amino acid metabolism via glutamate dehydrogenase that may affect the activity of aerobic respiration in the neutrophils. Using correlation analysis was found that the intensity of the neutrophils respiratory burst in patients with no subsequent complications depends on the activity of anaerobic glycolysis.
 Conclusion. The established differences in the state of the respiratory burst and the activity of enzymes in neutrophils in patients with WPP, in depending on the subsequent development of the sepsis, determine the possibility of developing the method of forecasting complications and developing immunoactive therapy in the postoperative period of WPP.

Utilizing predictive machine-learning modelling unveils feature-based risk assessment system for hyperinflammatory patterns and infectious outcomes in polytrauma.

Earlier research has identified several potentially predictive features including biomarkers associated with trauma, which can be used to assess the risk for harmful outcomes of polytraumatized patients. These features encompass various aspects such as the nature and severity of the injury, accompanying health conditions, immune and inflammatory markers, and blood parameters linked to organ functioning, however their applicability is limited. Numerous indicators relevant to the patients` outcome are routinely gathered in the intensive care unit (ICU) and recorded in electronic medical records, rendering them suitable predictors for risk assessment of polytraumatized patients. 317 polytraumatized patients were included, and the influence of 29 clinical and biological features on the complication patterns for systemic inflammatory response syndrome (SIRS), pneumonia and sepsis were analyzed with a machine learning workflow including clustering, classification and explainability using SHapley Additive exPlanations (SHAP) values. The predictive ability of the analyzed features within three days after admission to the hospital were compared based on patient-specific outcomes using receiver-operating characteristics. A correlation and clustering analysis revealed that distinct patterns of injury and biomarker patterns were observed for the major complication classes. A k-means clustering suggested four different clusters based on the major complications SIRS, pneumonia and sepsis as well as a patient subgroup that developed no complications. For classification of the outcome groups with no complications, pneumonia and sepsis based on boosting ensemble classification, 90% were correctly classified as low-risk group (no complications). For the high-risk groups associated with development of pneumonia and sepsis, 80% of the patients were correctly identified. The explainability analysis with SHAP values identified the top-ranking features that had the largest impact on the development of adverse outcome patterns. For both investigated risk scenarios (infectious complications and long ICU stay) the most important features are SOFA score, Glasgow Coma Scale, lactate, GGT and hemoglobin blood concentration. The machine learning-based identification of prognostic feature patterns in patients with traumatic injuries may improve tailoring personalized treatment modalities to mitigate the adverse outcomes in high-risk patient clusters.

Investigating the impact of human blood metabolites on the Sepsis development and progression: a study utilizing two-sample Mendelian randomization.

Existing data suggests a potential link between human blood metabolites and sepsis, yet the precise cause-and-effect relationship remains elusive. By using a two-sample Mendelian randomization (MR) analysis, this study aims to establish a causal link between human blood metabolites and sepsis. A two-sample MR analysis was employed to investigate the relationship between blood metabolites and sepsis. To assess the causal connection between sepsis and human blood metabolites, five different MR methods were employed, A variety of sensitivity analyses were conducted, including Cochrane's Q test, MR-Egger intercept test, MR-PRESSO and leave-one-out (LOO) analysis. In order to ensure the robustness of the causal association between exposure and outcome, the Bonferroni adjustment was employed. Additionally, we conducted analyses of the metabolic pathways of the identified metabolites using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Small Molecule Pathway Database (SMPDB) database. The MR analysis revealed a total of 27 metabolites (16 known and 11 unknown) causally linked to the development and progression of sepsis. After applying the Bonferroni correction, 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) remained significant in relation to 28-day all-cause mortality in sepsis. By pathway enrichment analysis, we identified four significant metabolic pathways. Notably, the Alpha Linolenic Acid and Linoleic Acid metabolism pathway emerged as a pivotal contributor to the occurrence and progression of sepsis. This study provides preliminary evidence of causal associations between human blood metabolites and sepsis, as ascertained by MR analysis. The findings offer valuable insights into the pathogenesis of sepsis and may provide insight into preventive and therapeutic approaches.

Bioinformatics reveals diagnostic potential of cuproptosis-related genes in the pathogenesis of sepsis

BackgroundMultiple modes of cell death occur during the development of sepsis. Among these patterns, cuproptosis has recently been identified as a regulated form of cell death. However, its impact on the onset and progression of sepsis remains unclear. MethodWe screened a dataset of gene expression profiles from patients with sepsis using the GEO database. Survival analysis was performed to analyze the relationship between cuproptosis-related genes (CRGs) and prognosis. Hub genes were identified through univariate Cox regression analysis. The diagnostic value of hub genes in sepsis was tested in both training sets (GSE65682) and validation sets (GSE134347). To examine the association between hub genes and immune cells, single-sample gene set enrichment analysis (ssGSEA) and Pearson correlation analysis were employed. Additionally, the CRGs were validated in a septic mouse model using real-time quantitative PCR (qRT-PCR) and immunohistochemistry (IHC). ResultsIn sepsis, most CRGs were upregulated, with only DLD and MTF1 downregulated. High expression of three genes (GLE, LIAS, and PDHB) was associated with better prognosis, but only two hub genes (LIAS, PDHB) reached statistical significance. The receiver operating characteristic (ROC) analysis for diagnosing sepsis showed LIAS had a range of 0.793–0.906, while PDHB achieved values of 0.882 and 0.975 in the training and validation sets, respectively. ssGSEA analysis revealed a lower number of immune cells in the sepsis group, and there was a correlation between immune cell population and CRGs (LIAS, PDHB). Analysis in the septic mouse model demonstrated no significant difference in mRNA expression levels and IHC staining between LIAS and PDHB in heart and liver tissues, but up-regulation was observed in lung tissues. Furthermore, the mRNA expression levels and IHC staining of LIAS and PDHB were down-regulated in renal tissues. ConclusionsCuproptosis is emerging as a significant factor in the development of sepsis. LIAS and PDHB, identified as potential diagnostic biomarkers for cuproptosis-associated sepsis, are believed to play crucial roles in the initiation and progression of cuproptosis-induced sepsis.

Protein Phosphorylation Mechanism of Mesenchymal Stem Cells in the Treatment of Sepsis: A Systematic Review and Meta-analysis.

The severity and mortality of sepsis are related to excessive inflammation and cytokine storm. Nevertheless, little is known about why sepsis has a significant increase in proinflammatory cytokine production, which leads to more severe inflammatory damage. Mesenchymal stem cells have achieved certain results in the treatment of sepsis, but the specific mechanism remains to be further clarified. Therefore, this paper will elaborate on the currently recognized mechanism of mesenchymal stem cells in the treatment of sepsis, the protein phosphorylation mechanism of sepsis inflammatory response, and the possibility that mesenchymal stem cells may block the occurrence and development of sepsis by regulating relevant pathways or protein phosphorylation. It provides a novel target for mesenchymal stem cells to prevent intervention or therapeutically block the development of sepsis.