Systemic Inflammatory Response Research Articles

Prediction of Poor Outcome Using the Urea to Albumin Ratio in Thoracic Empyema.

The prognostic performance of urea-to-albumin ratio (UAR) has been assessed in various pulmonary and nonpulmonary conditions, but never in thoracic empyema. Therefore, our aim was to determine whether this marker has the ability to predict outcome in such patients. A single-center retrospective study was conducted in a Clinic of Thoracic Surgery at a University Hospital between January 2021 and October 2023. A total of 84 patients who underwent emergency surgery due to thoracic empyema were involved. Serum levels of urea and albumin at admission were used to calculate UAR. We analyzed area under receiver operating characteristics (AUROC) curves of UAR, systemic inflammatory response syndrome (SIRS) and quick-sequential organ failure assessment (qSOFA), and compared their prognostic performance. The identified in-hospital mortality was 10.7%. The UAR showed the best ability to prognosticate mortality compared to qSOFA (AUROC = 0.828 vs 0.747) and SIRS (AUROC = 0.828 vs 0.676). We established a sensitivity of 87.5% and specificity of 74.2% at optimal cut-off value UAR > 51.1 for prediction of adverse outcome. In patients with thoracic empyema urea-to-albumin ratio showed significant prognostic performance and a potential for clinical application as a low cost and widely available predictor of death.

Hidradenitis suppurativa (HS), systemic inflammatory response syndrome and sepsis: a database study.

Hidradenitis suppurativa (HS) has unclear pathophysiology and etiology, but it is not an infectious disease. However, HS is frequently mistaken for an infection and HS patients are treated for recurrent bacterial abscesses, or admitted for sepsis. A systematic literature search that is published as a separate paper did not identify an index case that demonstrates that sepsis can originate in an HS lesions.1 However, since HS patients get admitted for sepsis anyway, we wanted to characterize them.

#1945 Comparative analysis of kidney transplantation modeled using precision-cut kidney slices and kidney transplantation in pigs

Abstract Background and Aims Kidney transplants are at risk for so far unavoidable ischemia-reperfusion injury. Several experimental kidney transplantation models are available to study this injury, but all have their own limitations. Here, we describe precision-cut kidney slices (PCKS) as a novel model of kidney ischemia-reperfusion injury in comparison with pig and human kidney transplantation. Method Following bilateral nephrectomy in pigs, we applied warm ischemia (1 h), cold ischemia (20 h) and a reperfusion period (4 h) to one whole kidney undergoing transplantation to a recipient pig and, in parallel, established PCKS undergoing ischemia and modeled reperfusion. Tissues were analyzed using standard histopathology assessment by two blinded pathologists, and bulk RNAseq with gene set enrichment analysis with comparison to human kidney biopsy gene sets obtained from Gene Expression Omnibus. Results Histopathological assessment revealed the presence of some but not all morphological features of tubular injury in PCKS as seen in pig kidney transplantation. RNAseq demonstrated that the majority of changes occurred after reperfusion only, with a partial overlap between PCKS and kidney transplantation, with some differences in transcriptional response attributable to systemic inflammatory responses and immune cell migration. Comparison of PCKS and pig kidney transplantation with RNAseq data from human kidney biopsies by gene set enrichment analysis revealed that both PCKS and pig kidney transplantation reproduced the post-reperfusion pattern of human kidney transplantation. In contrast, only post-cold ischemia PCKS and pig kidney partially resembled the gene set of human acute kidney injury. Conclusion Overall, the present study established that a PCKS protocol can model kidney transplantation and its reperfusion-related damage on a histological and a transcriptomic level. PCKS may thus expand the toolbox for developing novel therapeutic strategies against ischemia-reperfusion injury.

IRG1/itaconate alleviates acute liver injury in septic mice by suppressing NLRP3 expression and its mediated macrophage pyroptosis via regulation of the Nrf2 pathway

Sepsis, a systemic inflammatory response triggered by infection, has a considerably high mortality rate. However, effective prevention and intervention measures against sepsis remain insufficient. Therefore, this study aimed to investigate the mechanisms underlying the protective properties of immune response gene-1 (IRG1) and 4-Octyl itaconate (OI) during acute liver damage in mice with sepsis.A sepsis mouse model was established to compare wild-type and IRG1-/- groups. The impact of IRG1/Itaconate on pro- and anti-inflammatory cytokines was evaluated using J774A.1 cells. IRG1/Itaconate substantially reduced pro-inflammatory cytokines and increased the release of anti-inflammatory cytokines. It reduced pathological damage to liver tissues, preserved normal liver function, decreased the release of reactive oxygen species (ROS) and LDH, and enhanced the GSH/GSSG ratio. Moreover, IRG1 and itaconic acid activated the Nrf2 signaling pathway, regulating the expression of its downstream antioxidative stress-related proteins. Additionally, they inhibited the activity of NLRP3 inflammatory vesicles to suppress the expression of macrophage-associated pyroptosis signaling molecules.Our findings demonstrate that IRG1/OI inhibits NLRP3 inflammatory vesicle activation and macrophage pyroptosis by modulating the Nrf2 signaling pathway, thereby attenuating acute liver injury in mice with sepsis. These findings could facilitate the clinical application of IRG1/Itaconate to prevent sepsis-induced acute liver injury.

An interpretable machine learning model for predicting 28-day mortality in patients with sepsis-associated liver injury.

Sepsis-Associated Liver Injury (SALI) is an independent risk factor for death from sepsis. The aim of this study was to develop an interpretable machine learning model for early prediction of 28-day mortality in patients with SALI. Data from the Medical Information Mart for Intensive Care (MIMIC-IV, v2.2, MIMIC-III, v1.4) were used in this study. The study cohort from MIMIC-IV was randomized to the training set (0.7) and the internal validation set (0.3), with MIMIC-III (2001 to 2008) as external validation. The features with more than 20% missing values were deleted and the remaining features were multiple interpolated. Lasso-CV that lasso linear model with iterative fitting along a regularization path in which the best model is selected by cross-validation was used to select important features for model development. Eight machine learning models including Random Forest (RF), Logistic Regression, Decision Tree, Extreme Gradient Boost (XGBoost), K Nearest Neighbor, Support Vector Machine, Generalized Linear Models in which the best model is selected by cross-validation (CV_glmnet), and Linear Discriminant Analysis (LDA) were developed. Shapley additive interpretation (SHAP) was used to improve the interpretability of the optimal model. At last, a total of 1043 patients were included, of whom 710 were from MIMIC-IV and 333 from MIMIC-III. Twenty-four clinically relevant parameters were selected for model construction. For the prediction of 28-day mortality of SALI in the internal validation set, the area under the curve (AUC (95% CI)) of RF was 0.79 (95% CI: 0.73-0.86), and which performed the best. Compared with the traditional disease severity scores including Oxford Acute Severity of Illness Score (OASIS), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Systemic Inflammatory Response Syndrome (SIRS), and Acute Physiology Score III (APS III), RF also had the best performance. SHAP analysis found that Urine output, Charlson Comorbidity Index (CCI), minimal Glasgow Coma Scale (GCS_min), blood urea nitrogen (BUN) and admission_age were the five most important features affecting RF model. Therefore, RF has good predictive ability for 28-day mortality prediction in SALI. Urine output, CCI, GCS_min, BUN and age at admission(admission_age) within 24 h after intensive care unit(ICU) admission contribute significantly to model prediction.

The Surgical Stress Response and Anesthesia: A Narrative Review.

The human physiological response "to stress" includes all metabolic and hormonal changes produced by a traumatic event at the micro or macro cellular levels. The main goal of the body's first response to trauma is to keep physiological homeostasis. The perioperative non-specific adaptation response can sometimes be detrimental and can produce systemic inflammatory response syndrome (SIRS), characterized by hypermetabolism and hyper catabolism. We performed a narrative review consisting of a description of the surgical stress response's categories of changes (neurohormonal and immunological response) followed by reviewing methods found in published studies to modulate the surgical stress response perioperatively. We described various preoperative measures cited in the literature as lowering the burden of surgical trauma. This article revises the anesthetic drugs and techniques that have an impact on the surgical stress response and proven immune-modulatory effects. We also tried to name present knowledge gaps requiring future research. Our review concludes that proper preoperative measures, adequate general anesthetics, multimodal analgesia, early postoperative mobilization, and early enteral nutrition can decrease the stress response to surgery and ease patient recovery. Anesthetics and analgesics used during the perioperative period may modulate the innate and adaptive immune system and inflammatory system, with a consecutive impact on cancer recurrence and long-term outcomes.

The relationship between the comprehensive blood inflammation indexes and stage I pneumoconiosis and its combined lung infections

Objective: To analyze the comprehensive blood inflammation index of the patients with stage I pneumoconiosis complicated with pulmonary infection, and to explore its value in predicting the patients' disease. Methods: In September 2023, 83 patients with stage I pneumoconiosis who were treated in Tianjin Occupational Diseases Precaution and Therapeutic Hospital from November 2021 to August 2023 were selected and divided into non-infected group (56 cases) and infected group (27 cases) according to whether they were combined with lung infection. Workers with a history of dust exposure but diagnosed without pneumoconiosis during the same period were selected as the control group (65 cases) . By referring to medical records and collecting clinical data such as gender, age, occupational history, past medical history, hematology testing, the differences in the comprehensive blood inflammation indexes among the three groups were compared, ROC curve was drawn, and the relationship between comprehensive blood inflammation indexes and stage I pneumoconiosis and its combined lung infection was analyzed. Results: There were significtant differences in the number of neutrophils (N) , the number of lymphocytes (L) , the number of monocytes (M) , C-reactive protein (CRP) , the neutrophil to lymphocyte ratio (NLR) , the monocyte to lymphocyte ratio (MLR) , the platelet to lymphocyte ratio (PLR) , the systemic immune-inflammatory index (SII) , the systemic inflammation response index (SIRI) , the aggregate index of systemic inflammation (AISI) , the derived neutrophil to lymphocyte ratio (dNLR) , the neutrophil to lymphocyte and platelet ratio (NLPR) , and the C-reactive protein to lymphocyte ratio (CLR) (P<0.05) . Compared with the control group, MLR, SIRI and AISI in the non-infected group were significantly increased (P<0.05) . NLR, MLR, PLR, SII, SIRI, AISI, dNLR, NLPR, CLR were significantly increased (P<0.05) . Compared with the non-infected group, NLR, PLR, SII, SIRI, AISI, dNLR, NLPR and CLR were significantly increased in the infected group (P<0.05) . ROC analysis showed that NLR, MLR, PLR, SII, SIRI and AISI had a certain predictive capability for stage I pneumoconiosis (P<0.05) , among which MLR had the highest efficacy, with an AUC of 0.791 (95% CI: 0.710-0.873) , the cut-off value was 0.18, the sensitivity was 71.4%, and the specificity was 78.5%. NLR, MLR, PLR, SII, SIRI, AISI, dNLR, NLPR and CLR all had a certain predictive capability forstage I pneumoconiosis combined lung infection (P<0.05) , among which CLR had the highest efficacy, with an AUC of 0.904 (95%CI: 0.824~0.985) , the cut-off value was 5.33, sensitivity was 77.8%, specificity was 98.2%. Conclusion: The comprehensive blood inflammation index may be an auxiliary predictor of stage I pneumoconiosis and its combined lung infections.

Systemic immune-inflammation index upon admission correlates to post-stroke cognitive impairment in patients with acute ischemic stroke.

The purpose of this prospective study was to evaluate the association of systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), with PSCI in patients with acute ischemic stroke (AIS). First-onset AIS patients were consecutively included from January 1, 2022 to March 1, 2023. The baseline information was collected at admission. Fasting blood was drawn the next morning. Cognitive function was assessed by the Montreal Cognitive Assessment (MoCA) 3 months after onset. Logistic regression analysis was performed to explore the correlation between SII, SIRI, and PSCI. Receiver operating characteristic (ROC) was conducted to evaluate the predictive ability of SII. 332 participants were recruited, and 193 developed PSCI. Compared with patients without PSCI, the patients with PSCI had higher SII (587.75 (337.42, 988.95) vs. 345.66 (248.44, 572.89), P<0.001) and SIRI (1.59 (0.95, 2.84) vs. 1.02 (0.63, 1.55), P=0.007). SII and SIRI negatively correlated with MoCA scores (both P<0.05). The multivariable logistic regression analysis indicated that SII was independently associated with PSCI (P<0.001), while SIRI was not. The optimal cutoff for SII to predict PSCI was 676.83×109/L. A higher level of SII upon admission was independently correlated to PSCI three months later in AIS patients.

A Siglec3-like lectin from Nile tilapia (Oreochromis niloticus): Transcriptional profiling upon Streptococcus agalactiae infection and its potential role in immune escape

Siglec-3, also known as CD33, is a type of sialic acid binding immunoglobulin-like lectin that plays a role in regulating cellular activation in the innate immune system and subsequent inflammatory responses. In this study, we cloned the cDNA encoding OnSiglec3-like ORF sequence (1170 bp) in Nile tilapia, contained two Ig-like domains in the extracellular region and one inhibitory ITIM-like motif in the intracellular region. Through qRT-PCR analysis, we found that the mRNA of OnSiglec3-like lectin was highly expressed in the brain and head kidney. When challenged with Streptococcus agalactiae both in vivo and in vitro, we observed a significant up-regulation in the expression of OnSiglec3-like lectin in the head kidney tissues and leukocytes, respectively. Additionally, we investigated the interaction between a recombinant extracellular region protein (referred to as (r)exSiglec3-like protein) and three different phenotypes of S. agalactiae: WT (wild type), ∆cps (cps-deficient mutant), and ∆neuA (sia-deficient mutant) using ELISA. We found that the exOnSiglec3-like protein, when combined with RNA interference and bacterial infection, significantly enhanced the phagocytic ability against S. agalactiae. Furthermore, the expression of four common inflammatory factors (OnIL-6, OnIL-10, OnTNF-α, and OnTGF-β) showed a significant up-regulation. Overall, this study suggests that OnSigelc3-like lectin may play a role in host defence against bacterial infection and mediate immune escape in Nile tilapia.

Drosophila models of the anti‐inflammatory and anti‐obesity mechanisms of kombucha tea produced by Camellia sinensis leaf fermentation

AbstractKombucha tea is a traditional beverage originating from China and has recently gained popularity worldwide. Kombucha tea is produced by the fermentation of tea leaves and is characterized by its beneficial properties and varied chemical content produced during the fermentation process, which includes organic acids, amino acids, vitamins, minerals, and other biologically active compounds. Kombucha tea is often consumed as a health drink to combat obesity and inflammation; however, the bioactive effects of kombucha tea have not been thoroughly researched. In this study, we reveal the underlying mechanisms of the beneficial properties of kombucha tea and how they protect against obesity and inflammation by studying Drosophila models. We established an inflammatory Drosophila model by knocking down the lipid storage droplet‐1 gene, a human perilipin‐1 ortholog. In this model, dysfunction of lipid storage droplet‐1 induces inflammation by enhancing the infiltration of hemocytes into adipose tissues, increasing reactive oxygen species production, elevating levels of proinflammatory cytokines, and promoting the differentiation of hemocytes into macrophages. These processes are regulated by the c‐Jun N‐terminal Kinase (JNK) pathway. Using this unique Drosophila model that mimics mammalian inflammation, we verified the beneficial effects of kombucha tea on reducing tissue inflammation. Our data confirms that kombucha tea effectively improves inflammatory conditions by suppressing the expression of cytokines and proinflammatory responses induced by lipid storage droplet‐1 dysfunction. It was found that kombucha tea consumption alleviated the production of reactive oxygen species and activated the JNK signaling pathway, signifying its potential as an anti‐inflammatory agent against systemic inflammatory responses connected to the JNK pathway. Kombucha tea reduced triglyceride accumulation by increasing the activity of Brummer (a lipase), thereby promoting lipolysis in third‐instar larvae. Therefore, kombucha tea could be developed as a novel, functional beverage to protect against obesity and inflammation. Our study also highlights the potential use of this innovative model to evaluate the effects of bioactive compounds derived from natural products.

Lactate dynamics in paediatric patients with severe sepsis: insights from a prospective cohort study

BackgroundSepsis is an infection-related systemic inflammatory response that often leads to elevated lactate levels. Monitoring lactate levels during severe sepsis is vital for influencing clinical outcomes. The aim of this study was to assess the association between plasma lactate levels and mortality in children with severe sepsis or septic shock.MethodsThe current prospective study was conducted in the PICU of University Children’s Hospital. The International Paediatric Sepsis Consensus Conference criteria for Definitions of Sepsis and Organ Failure in 2005 were used to diagnose patients with sepsis. We measured plasma lactate levels upon admission (Lac H0) and 6 h later (Lac H6). The static indices included the absolute lactate values (Lac H0 and Lac H6), while the dynamic indices included the delta-lactate level (ΔLac) and the 6-hour lactate clearance. The 6-hour lactate clearance was calculated using the following formula: [(Lac H0–Lac H6)100/Lac H0]. ΔLac was calculated as the difference between the Lac H0 and Lac H6 levels. Patient survival or death after a PICU stay was the primary outcome.ResultsA total of 46 patients were included in this study: 25 had septic shock, and 21 had severe sepsis. The mortality rate was 54.3%. The Lac H0 did not significantly differ between survivors and nonsurvivors. In contrast, the survivors had significantly lower Lac H6 levels, higher ΔLac levels, and higher 6-hour lactate clearance rates than nonsurvivors. Lactate clearance rates below 10%, 20%, and 30% were significantly associated with mortality. The best cut-off values for the lactate clearance rate and Lac H6 for the prediction of mortality in the PICU were < 10% and ≥ 4 mmol/L, respectively. Patients with higher Lac H6 levels and lower lactate clearance rates had significantly higher PICU mortality based on Kaplan–Meier survival curve analysis.ConclusionsThis study highlights the significance of lactate level trends over time for the prediction of mortality in the PICU in patients with severe sepsis or septic shock. Elevated lactate levels and decreased lactate clearance six hours after hospitalisation are associated with a higher mortality rate.

Association between blood inflammatory indices and heart failure: a cross-sectional study of NHANES 2009-2018

Background Inflammation plays a pivotal role in the pathogenesis of heart failure (HF). This study was aimed to the potential association between complete blood cell count (CBC)-derived inflammatory biomarkers and HF. Methods Data from the National Health and Nutrition Examination Survey (NHANES) 2009-2018 were utilised. We evaluated the associations between HF and five systemic inflammation markers derived from CBC: systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). Demographic characteristics, physical examinations, and laboratory data were systematically collected for comparative analysis between HF and non-HF individuals. Fitted smoothing curves and threshold effect analysis delineated the relationship. In addition, Spearman correlation and subgroup analyses were further conducted. Results A total of 26,021 participants were categorised into HF (n = 858) and non-HF (n = 25,163) groups. After adjusting for confounding variables, SIRI, NLR, and MLR had significant positive correlations with the risk of HF. Participants in the highest quarter groups of SIRI, NLR, and MLR showed a increased risk of developing HF compared to those in the lowest quarter group. Furthermore, subgroup and sensitivity analyses indicated that SIRI, NLR, and MLR had a stronger correlation to HF (all p < 0.05). Smoothing curve fitting highlighted a nonlinear relationship between CBC-derived inflammatory biomarkers and HF. Conclusions Our results illustrated a significant association between elevated levels of SIRI, NLR, and MLR and an increased risk of HF. SIRI, NLR, and MLR could potentially serve as systemic inflammation hazard markers for HF.

Bleeding and thrombotic events and intensity of heparin therapy in the two first waves of COVID-19.

A systemic inflammatory response occurs during SARS-CoV2 infection and is associated with hypercoagulability and thrombotic events. From March 2020 in our hospital different dosages of low-molecular weight heparin (LMWH) were introduced according to the level of patient care intensity. Because bleeding episodes occurred in hospitalized COVID-19 patients on heparin, the dosage of LMWH at the end of first wave was tailored on the severity of COVID-19. The aim of this study is to describe bleeding and thrombotic events in patients hospitalized with SARS-CoV2 infection on LMWH therapy in the two waves of COVID-19 and analyze the factors associated with these events. Among 1143 patients enrolled in the COVID-19 Network registry, 912 were included in the analysis, 537 of them admitted during the first wave and 375 during the second. Bleeding events were 30 (3.3%): 22 (2.4%) major and 8 (0.9%) non-major. Arterial and venous thrombotic events were 6 (0.7%) and 24 (2.6%). The incidence of venous thrombotic events was higher in the first than in the second wave (0.29% [95% CI 0.20-0.45] events/day vs. 0.05% [95% CI 0.02-0.16]), with a 71% risk reduction (95% CI 22%-94%). The incidence of bleeding was 0.33% (95% CI 0.22-0.50) vs 0.14% events/day (95% CI 0.07-0.28), with no statistical between-wave difference (HR 0.41 95% CI 0.16-1.08). After adjusting for the competing risks of death and comorbidities, patients in the second wave had lower odds to have thrombotic events than in the first wave (0.24 HR [95% C.I. 0.07-0.89]). In this retrospective study on COVID-19 we found a low rate of hemorrhagic and thrombotic events, that may be explained by the absence in the case material of patients admitted to intensive care unit.

PP-039 COVID-19 during pregnancy and systemic inflammatory response syndrome

PP-039 COVID-19 during pregnancy and systemic inflammatory response syndrome

Does remote ischemic preconditioning affect the systemic inflammatory response by modulating presepsin levels?

We investigated the effect of Remote Ischemic Preconditioning (RIPC) on the inflammatory response during CPB by means of serum presepsin levels at preoperative and postoperative 1st and 24th h. In this prospective, randomized, cross-sectional study we included 81 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). Patients were randomized and RIPC was applied to 40 patients in the study group before anesthesia. The remaining 41 patients were determined as the control group. The relationships between RIPC and factors such as presepsin, C-reactive protein (CRP), and leukocyte levels were investigated. There was no significant difference between the groups in postoperative leukocyte and CRP values (p = 0.52, p = 0.13, respectively). When the preoperative and postoperative first hour presepsin values of the patients were compared, no significant difference was found in the control group (p = 0.17), but a significant difference was found in the study group (p < 0.05). When the presepsin values were compared between the groups, a significant difference was found only in the postoperative first hour value (p < 0.05). It was observed that RIPC application caused to increase the presepsin levels in the postoperative first hour significantly in the study group (p < 0.05).

Association of systemic inflammatory response index with bone mineral density, osteoporosis, and future fracture risk in elderly hypertensive patients

ABSTRACT Objectives This study sought to investigate the relationship between the systemic inflammatory response index (SIRI) and bone mineral density (BMD), osteoporosis, and future fracture risk in elderly hypertensive patients. Methods Elderly hypertensive patients (age ≥60 years) who attended our hospital between January 2021 and December 2023 and completed BMD screening were included in the study. Analyses were performed with multivariate logistic and linear regression. Results The multiple linear regression indicated that SIRI levels were significantly negatively correlated with lumbar 1 BMD (β = -0.15, 95% CI: −0.24, −0.05), lumbar 2 BMD (β = -0.15, 95% CI: −0.24, −0.05), lumbar 3 BMD (β = -1.35, 95% CI: −0.23, −0.02), lumbar 4 BMD (β = -0.11, 95% CI: −0.30, −0.10), femur neck BMD (β = -0.11, 95% CI: −0.18, −0.05) and Ward’s triangle BMD (β = -0.12, 95% CI: −0.20, −0.05) among elderly hypertensive patients, after fully adjusting for confounders. Furthermore, we observed that SIRI was positively associated with future fracture risk in elderly hypertensive patients. Specifically, SIRI was associated with an increased risk of major osteoporotic fractures (β = 0.33) and hip fractures (β = 0.25). The logistic regression analysis indicated that there is an association between the SIRI level and an increased risk of osteoporosis (OR = 1.60, 95% CI = 1.37, 1.87), after fully adjusting for confounders. Conclusions Our findings indicate a potential association between SIRI and BMD, osteoporosis, and the risk of future fractures in elderly hypertensive patients. However, further studies are warranted to confirm these findings.

β-hydroxybutyrate alleviates neurological deficits by restoring glymphatic and inflammation after subarachnoid hemorrhage in mice

BackgroundBoth glymphatic system dysfunction and inflammatory response aggravate neurological dysfunction after subarachnoid hemorrhage (SAH). Studies have shown that β-hydroxybutyrate (BHB) may mitigate painful diabetic neuropathy (PDN) by upregulating SNTA1 expression and reinstating AQP4 polarity. However, the potential of BHB to ameliorate glymphatic system function and inflammatory response in SAH mice remains uncertain. MethodsThe SAH models were constructed by injection of arterial blood into cisterna Magana. Three groups of C57 mice were randomly assigned: Sham, SAH, and BHB. All mice were subjected to neurological function assessment, western blot, immunofluorescence double staining, and RNA-seq. Glymphatic system function was examined with tracer and immunofluorescence double staining, and the differential genes were examined with RNA-seq. In addition, the expression of related inflammation was detected. ResultsCompared with the SAH group, BHB reinstated AQP4 polarization by upregulating SNTA1 protein to enhance the glymphatic system. According to RNA-seq, the different genes were primarily connected to microglia activation, astrocytes, and inflammation. Western blot and immunofluorescence further confirmed that the related inflammatory protein expression levels were upregulated. BHB attenuated neuroinflammation after SAH. Ultimately, it can mitigate the neurological deficits in SAH mice. ConclusionThe study reveals a novel mechanism that BHB treatment mitigates neurologic impairment in SAH mice. We propose that BHB may play a neuroprotective effect by enhancing glymphatic system function and attenuating neuroinflammatory subarachnoid hemorrhage.

U-shaped relationship found between fibrinogen-to-albumin ratio and systemic inflammation response index in osteoporotic fracture patients

The relationship between the Systemic Inflammatory Response Index (SIRI) and the Fibrinogen-to-albumin ratio (FAR) has not been extensively investigated. The objective of this study was to determine the independent relationship between FAR and SIRI in people with osteoporotic fractures (OPF). A cross-sectional study was conducted using retrospective data from 3431 hospitalized OPF patients. The exposure variable in this study was the baseline FAR, while the outcome variable was the SIRI. Covariates, including age, gender, BMI, and other clinical and laboratory factors, were adjusted. Cross-correlation analysis and linear regression models were applied. The generalized additive model (GAM) investigated non-linear relationships. Adjusted analysis revealed an independent negative association between FAR and SIRI in OPF patients (β = − 0.114, p = 0.00064, 95% CI − 0.180, − 0.049). A substantial U-shaped association between FAR and SIRI was shown using GAM analysis (p < 0.001). FAR and SIRI indicated a negative association for FAR below 6.344% and a positive correlation for FAR over 6.344%. The results of our study revealed a U-shaped relationship between SIRI and FAR. The lowest conceivable FAR for a bone-loose inflammatory disease might be 6.344%, suggesting that this has particular significance for the medical diagnosis and therapy of persons with OPF. Consequently, the term "inflammatory trough" is proposed. These results offer fresh perspectives on controlling inflammation in individuals with OPF and preventing inflammatory osteoporosis.

Heart rate and oxygen saturation patterns in very low birth weight infants with early onset sepsis and histologic chorioamnionitis.

Chorioamnionitis and early onset sepsis (EOS) in very low birth weight (VLBW,< 1500 g) infants may cause a systemic inflammatory response reflected in patterns of heart rate (HR) and oxygenation measured by pulse oximetry (SpO2). Identification of these patterns might inform decisions about duration of antibiotic therapy after birth. Compare early HR and SpO2 patterns in VLBW infants with or without early onset sepsis (EOS) or histologic chorioamnionitis (HC). Retrospective study of placental pathology and HR and SpO2 in the first 72 h from birth in relation to EOS status for inborn VLBW NICU patients 2012-2019. Among 362 VLBW infants with HR and SpO2 data available, clinical, or culture-positive EOS occurred in 91/362 (25%) and HC in 81/355 (22%). In univariate analysis, EOS was associated with higher mean HR, lower mean SpO2, and less negative skewness of HR in the first 3 days after birth. HC was associated with higher standard deviation and skewness of HR but no difference in SpO2. In multivariable modeling, significant risk factors for EOS were mean HR, gestational age, HC, mean SpO2, and skewness of SpO2. HR and SpO2 patterns differ shortly after birth in VLBW infants exposed to HC or with EOS, likely reflecting a systemic inflammatory response.

Associations of CBC-Derived inflammatory indicators with sarcopenia and mortality in adults: evidence from Nhanes 1999 ∼ 2006

BackgroundIt has been proposed that inflammation plays a role in the development of sarcopenia. This study aimed to investigate the links of complete blood cell count (CBC) parameters and CBC-derived inflammatory indicators with sarcopenia and mortality.MethodsData pertaining to sarcopenia were extracted from the 1999–2006 National Health and Nutrition Examination Survey (NHANES), and mortality events were ascertained through the National Death Index up to December 31, 2019. The CBC-derived inflammatory indicators assessed in this study included the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-monocyte to lymphocyte ratio (NMLR), systemic inflammatory response index (SIRI), and systemic immune-inflammation index (SII). The prognostic significance of these CBC-derived inflammatory indicators was evaluated using the random survival forests (RSF) analysis.ResultsThe study encompassed a cohort of 12,689 individuals, among whom 1,725 were diagnosed with sarcopenia. Among individuals with sarcopenia, 782 experienced all-cause mortality, and 195 succumbed to cardiovascular causes. Following adjustment for confounding variables, it was observed that elevated levels of NLR, dNLR, NMLR, SIRI, and SII were associated with an increased prevalence of sarcopenia. Among participants with sarcopenia, those in the highest quartile of NLR (HR = 1.336 [1.095–1.631]), dNLR (HR = 1.274 [1.046–1.550]), MLR (HR = 1.619 [1.290–2.032]), NMLR (HR = 1.390 [1.132–1.707]), and SIRI (HR = 1.501 [1.210–1.862]) exhibited an elevated risk of all-cause mortality compared to those in the lowest quartile of these inflammation-derived indicators. These associations were similarly observed in cardiovascular mortality (HR = 1.874 [1.169–3.003] for MLR, HR = 1.838 [1.175–2.878] for SIRI). The RSF analysis indicated that MLR exhibited the highest predictive power for both all-cause and cardiovascular mortality among individuals with sarcopenia.ConclusionsOur findings underscore the association between CBC-derived inflammatory indicators and mortality in adults with sarcopenia. Of note, MLR emerged as the most robust predictor of all-cause and cardiovascular mortality in this population.