Systemic Inflammatory Response In Patients Research Articles

Interactions of humoral immune response indicators and parameters of systemic inflammatory response in patients with post-COVID-19 syndrome

Objective. To assess the state of the systemic inflammatory response and humoral immune response in middle-aged patients came through COVID-19 infection in mild and moderate severity. Materials and methods. A cohort single-center study involving 83 patients came through COVID-19 infection in mild and moderate severity (women - 69.9% (58 patients), men - 30.1% (25 patients); median age 53 years [49; 56] was conducted over the period 2022-2023. All patients underwent clinical examination, evaluation of humoral response with determination of IgG and IgM antibodies to SARS-CoV-2 virus, as well as concentration of interleukins: interleukin-1β, interleukin-4, interleukin-6, interleukin-8, interleukin-10, high-sensitivity C-reactive protein, tumour necrosis factor α, transforming growth factor β1 and procalcitonin concentrations. Patients were divided into three groups: 1-3 months; 3-6 months; and 6 months to 1 year after COVID-19 infection. Results. Within a year the percentage of IgM-positive patients in all patient groups was about a quarter (25 %, 21 % and 25 % respectively). While remaining within the reference values for the whole group, procalcitonin and interleukin-10 levels in the selected cohort exceeded those of the test-negative cohort (p = 0.0053 and p = 0.0044, respectively), which we considered as persistent chronic compensated inflammation. Conclusion. A quarter of patients who came through COVID-19 infection in mild and moderate severity have persistently positive IgM levels for a year, combined with proinflammatory status according to systemic inflammatory response parameters.

The CRP troponin test (CTT) stratifies mortality risk in patients with non-ST elevation myocardial infarction (NSTEMI).

The C-reactive protein (CRP)-troponin-test (CTT) comprises simultaneous serial measurements of CRP and cardiac troponin and might reflect the systemic inflammatory response in patients with acute coronary syndrome. We sought to test its ability to stratify the short- and long-term mortality risk in patients with non-ST elevation myocardial infarction (NSTEMI). We examined 1,675 patients diagnosed with NSTEMI on discharge who had at least two successive measurements of combined CRP and cardiac troponin within 48 h of admission. A tree classifier model determined which measurements and cutoffs could be used to best predict mortality during a median follow-up of 3 years [IQR 1.8-4.3]. Patients with high CRP levels ( > 90th percentile, >54 mg/L) had a higher 30-day mortality rate regardless of their troponin test findings (16.7% vs. 2.9%, p < 0.01). However, among patients with "normal" CRP levels ( < 54 mg/L), those who had high troponin levels ( > 80th percentile, 4,918 ng/L) had a higher 30-day mortality rate than patients with normal CRP and troponin concentrations (7% vs. 2%, p < 0.01). The CTT test result was an independent predictor for overall mortality even after adjusting for age, sex, and comorbidities (HR = 2.28 [95% CI 1.56-3.37], p < 0.01 for patients with high troponin and high CRP levels). Early serial CTT results may stratify mortality risk in patients with NSTEMI, especially those with "normal" CRP levels. The CTT could potentially assess the impact of inflammation during myocardial necrosis on the outcomes of patients with NSTEMI and identify patients who could benefit from novel anti-inflammatory therapies.

Biomarkers of peripheral blood neutrophil extracellular traps in the diagnosis and progression of malignant tumors.

The mortality rate associated with malignant tumors remains high and there is a lack of effective diagnostic and tumor progression markers. Neutrophil extracellular traps (NETs) can promote tumor-associated thrombosis, invasive metastasis, and inflammatory responses, but there is a lack of research on the value of measuring NETs in the peripheral blood of patients with malignancies. We included 263 patients with malignancies (55 gliomas, 101 ovarian, 64 colorectal, and 43 lung cancers) and 75 healthy controls in this study. We compared the levels of citrullinated histone H3 (citH3), cell-free DNA (cfDNA), and systemic inflammation-related parameters, including neutrophils, lymphocytes, monocytes, platelets, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune inflammation index, and systemic inflammation response index. We assessed the value of changes in NETs in peripheral blood to determine the diagnosis, venous thromboembolism, clinical staging, and systemic inflammatory response in patients with malignancy. The levels of citH3 and cfDNA in peripheral blood can distinguish between healthy controls and tumor patients. The levels of citH3 and cfDNA before clinical intervention did not predict the risk of combined venous thromboembolism in oncology patients in the short-term after clinical intervention. The levels of citH3, cfDNA, and systemic inflammation-related parameters in the peripheral blood of tumor patients increased with the clinical stage. There was a correlation between cfDNA levels in peripheral blood and systemic inflammation-related parameters in tumor patients, and this correlation was more significant in patients with advanced tumors. Changes in NETs in the peripheral blood differ between healthy controls and patients with malignant tumors. NETs may be involved in tumor-induced systemic inflammatory responses through interaction with circulating inflammatory cells, thus promoting tumor progression. NETs may be used as markers to assist in the diagnosis and progression of tumor malignancy.

Антропометрические характеристики и особенности системного воспалительного ответа у пациенток с эндометриозом

Abstract Aim. To assess the relationship between cytokine levels and body mass index (BMI) in women with ovarian endometriomas. Design. A prospective cohort study. Materials and methods. The study included 46 women referred for surgical treatment (laparoscopy, cystectomy) due to ovarian endometriomas. Peritoneal fluid in a volume of 2–5 ml was collected intraoperatively from all women for the study; on the eve of the operation, saliva was also collected from all women. In biological fluids, we assessed the level of interleukins (IL) and vascular endothelial growth factor. Results. A statistically significant correlation was found between BMI and the level of IL-1 in saliva (r = 0.391, p = 0.015), as well as the level of IL-8 in peritoneal fluid (r = 0.311, p = 0.044). At the same time, a direct relationship was revealed between the level of BMI and the severity of chronic pelvic pain (r = 0.297, p = 0.046). In addition, we determined that there was an inverse relationship between the level of IL-8 in the peritoneal fluid and anti-Mullerian hormone (AMH) (r = –0.342, p = 0.026). Higher BMI in women with endometriomas was also associated with lower AMH (r = –0.478, p &lt; 0.001). Conclusion. In the presence of ovarian endometriosis, an increase in BMI is associated with a greater severity of chronic pelvic pain, which is associated with an increase in inflammatory mediators - a statistically significant direct relationship between BMI and the level of IL-1 in saliva and IL-8 in peritoneal fluid was revealed. In addition, a high BMI is associated with lower ovarian reserve rates. Further study of the cytokine profile in women with endometriosis depending on body weight may contribute to the development of new personalized therapy regimens. Key words: endometrioma, endometriosis, cytokines, chronic pelvic pain, infertility.

Systemic Inflammatory Patterns in Ovarian Cancer Patients: Analysis of Cytokines, Chemokines, and Microparticles.

To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses. We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry. Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1β), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks. The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.

The CRP Troponin Test (CTT) stratifies mortality risk in patients with Non-ST Elevation Myocardial Infarction (NSTEMI)

Abstract Introduction The CRP-Troponin test (CTT) comprises serial measurements of both CRP and cardiac troponin and might reflect the systemic inflammatory response in patients with acute coronary syndrome. Here, we sought to test the ability of the CTT to stratify the short and long-term mortality risk in patients with non-ST elevation myocardial infarction (NSTEMI). Materials and Methods We examined 1,675 patients who were diagnosed with NSTEMI on discharge and had at least two successive measurements of combined CRP and cardiac troponin (up to 6 h apart), all within the first 48 hours of admission. We used a tree classifier model to determine which measurements and cutoffs could be used to best predict mortality during a median follow-up period of 3 years [IQR 1.8–4.3] (Figure 1A). Results Patients with high CRP levels (above 90th percentile, &amp;gt;54 mg/L) had a higher 30-day mortality rate regardless of their troponin test status (Figure 1B). However, among patients with "normal" CRP levels (&amp;lt;54 mg/L), those who had high troponin levels (above the 80th percentile, 4,918 ng/L) had a higher 30-day mortality rate compared with patients with normal CRP and troponin concentrations; 7% vs. 2%, p&amp;lt;0.01 (Figure 1B). A multivariate cox regression analysis showed that the CTT test result was an independent predictor for overall mortality even after adjusting for age, sex, and existing co-morbidities (Figure 1C). Conclusion Early serial CTT results may stratify mortality risk in patients with NSTEMI, especially in those presenting with "normal" CRP levels. The CTT is a simple diagnostic tool that could potentially assess the impact of inflammation during myocardial necrosis on the outcomes of patients with NSTEMI. The CTT might be used to identify patients who could benefit from novel anti-inflammatory therapies following myocardial infarction.Figure 1

Relationship between systemic inflammatory response and hypercoagulation in patients with immuno-inflammatory rheumatic diseases

The relationship between the processes of coagulation and inflammation protects the organism from potentially dangerous biological agents. However, hyperinflammation leads to an increase in the procoagulation potential, and activation of hemostasis factors maintains the inflammatory process. This phenomenon is called “immunothrombosis” or “ thromboinflammation”. The study of thromboinflammatory mechanisms is an actual problem of modern medicine, because in the future it will help to improve the therapy of diseases, in the pathogenesis of which thromboinflammation plays a significant role. The aim: to carry out a comparative analysis of the severity of the systemic inflammatory response in patients with immuno- inflammatory rheumatic diseases depending on the manifestations of hypercoagulation.To achieve the aim, a comparative analysis of proinflammatory markers (IL-6, IL-8, IL-10, TNFα, sIL-2R, CRP, ECP, β2-microglobulin) in the blood of patients with immune-inflammatory rheumatic diseases (systemic lupus erythematosus, rheumatoid arthritis, reactive arthritis, ankylosing spondylitis, psoriatic arthritis, rheumatic heart disease) was performed. Based on these inflammatory markers according to the authors' original methodology, the integral index of systemic inflammatory response (SIR) — Reactivity Level (RL) — was calculated. The cohort was divided into 2 groups: with the presence of signs of hypercoagulation and without signs of hypercoagulation according to the presence of elevated D-dimer level (&gt; 500 ng/mL). Control group — healthy blood donors.The results of the study showed that SIR develops in patients with immuno-inflammatory rheumatic diseases regardless of the blood hemostatic potential. Patients with signs of hypercoagulation were characterized by higher values of most proinflammatory molecular markers, as well as increased integral level of SIR, which indicates a strong relationship between coagulation processes and inflammation at the systemic level. In addition, the probability of hypercoagulation increases with increasing severity of SIR (assessed by means of the integral index — RL). Thus, there is a transition of quantitatively more pronounced signs to a new qualitative level of pathological process development.The pathogenesis of immuno-inflammatory rheumatic diseases is characterized by the development of SIR (hypercytokinemia, acute phase response, intravascular leukocyte activation), the severity of which is closely related to intravascular microthrombosis.

Identification of the relationship between biomarkers of autophagy, apoptosis and inflammation in the acute period of atherothrombotic ischemic stroke

The postischemic inflammatory response plays a significant role in the pathogenesis of acute ischemic stroke (IS). It has been established that acute IS is accompanied by aseptic inflammation, which induces the activation of costimulatory molecules in the process of innate immunity response to brain tissue damage. The constantly progressive destruction of neuronal antigens contributes to an increase in the volume of the ischemic lesion. Evidence continues to accumulate indicating an important role of NLRP3-mediated inflammation in the pathogenesis of IS. It has been shown that autophagy is involved in the inflammatory cascade in acute IS. Many of the anti-inflammatory mechanisms mediated by autophagy in acute IS involve the key autophagic proteins Beclin-1, LC3, and p62. Experimental studies have shown that autophagy suppresses the activation of NLRP3 inflammation. Data on cross interactions between apoptosis and autophagy in the pathogenesis of IS are still controversial. The aim of the study was to evaluate the relationship between biomarkers of autophagy, inflammation, and apoptosis in the dynamics of the acute period of atherothrombotic IS. The article presents the results of a dynamic study of the serum concentration of the key autophagy biomarkers Beclin-1, LC3 and p62, apoptosis indicators Bcl-2 and p53, pro-inflammatory cytokines IL-1β, TNFα, IL-8, IL-18 which are involved in postischemic neuroinflammation. A statistically significant increase in the studied parameters was established in comparison with the control group. The maximum increase in the studied biomarkers is noted on the 1st day after the development of ischemia in patients with a severe course of the disease. The relationship between autophagy activity, apoptosis biomarkers, and some indicators of the systemic inflammatory response in patients with moderate and severe atherothrombotic stroke was revealed. The results obtained confirm the literature data on the involvement of autophagy in the regulation of the postischemic inflammatory response.

Effect of the Pre-Operative Systemic Inflammatory Response on Outcomes Following Carotid Endarterectomy for Symptomatic Carotid Stenosis

Objective: Stroke accounts for over 100 000 acute hospital presentations per year in the UK, and approximately 4 500 carotid endarterectomies are performed annually in the UK.1 This is despite a relative paucity of cases performed for asymptomatic carotid stenosis, in comparison with other countries.1 Periprocedural stroke and death rates have fallen in recent years,2 although these remain notable risks necessitating careful patient selection and counselling. Chronic activation of the systemic inflammatory response (SIR) is prevalent in patients with atherosclerotic disease and influences both the pathogenesis and prognosis.3,4 The neutrophil:lymphocyte and platelet:lymphocyte ratios (NLR, PLR) are markers of the SIR, and are reported to provide prognostic value in patients with acute stroke,5 and in patients undergoing carotid endarterectomy.6 The Modified Glasgow Prognostic Score (mGPS) is calculated from C-reactive protein (CRP) and albumin and was originally described in patients with cancer.7 More recently mGPS has been shown to provide prognostic value in non-cancer patient groups.8 mGPS is representative of an alternative pathway activating the SIR and is not reported in relation to carotid endarterectomy outcomes. The present study describes experience of the prognostic value of these pre-operative markers of SIR in patients undergoing carotid endarterectomy.

Evaluation of the systemic inflammatory response in patients with a spinal synovial cyst or lumbar disc herniation

Aims: This study aimed to determine whether a systemic inflammatory response occurs in patients with spinal synovial cysts (SSC) and patients with lumbar disc herniation. Methods: Patients who underwent surgery for SSC or lumbar disc herniation between 2016-2022 were included in the study. To compare the results of these patients, patients who applied to the outpatient clinic due to headaches but did not find any abnormal findings in the radiological examinations were also included. Age, gender, duration of stay in the hospital, comorbidity, and histopathological evaluation results were recorded for all patients. The lumbar T2 weighted MR sagittal and axial images obtained on admission to the hospital were examined. The venous blood samples taken from the patients on first admission to the hospital were analyzed biochemically. Results: There was no statistical difference between the three groups regarding age, gender, and blood biochemistry parameters. Furthermore, no statistical difference was found between SSC patients and patients with lumbar disc herniation in age, gender, cyst or herniated disc localization levels, comorbidity, and blood biochemistry analysis results. Correlation analysis for the findings of all patients revealed that no parameters were correlated with the study groups. ROC-Curve test and Logistic Regression tests showed that no parameter could be a predictive marker in differentiating SSC from disc herniation. Conclusion: Study results demonstrated that neither SSC nor disc herniation caused a systemic inflammatory or allergic reaction in the patients. In addition, it was determined that no biochemical parameter could distinguish disc herniation from SSC.

Effect of sphincter of Oddi dysfunction on the abundance of biliary microbiota (biliary microecology) in patients with common bile duct stones.

Biliary calculi, a common benign disease of the gastrointestinal tract, are affected by multiple factors, including diet, lifestyle, living environment, and personal and genetic background. Its occurrence is believed to be related to a change in biliary microbiota. Approximately 10%-20% of symptomatic patients with cholecystolithiasis have choledocholithiasis, resulting in infection, abdominal pain, jaundice, and biliary pancreatitis. This study aimed to determine whether a dysfunction in the sphincter of Oddi, which controls the outflow of bile and separates the bile duct from the intestine, leads to a change in biliary microbiota and the occurrence of biliary calculi. Forty patients with cholecystolithiasis and choledocholithiasis were prospectively recruited. Bile specimens were obtained, and biliary pressure was measured during and after surgery. The collected specimens were analyzed with 16S rRNA gene to characterize the biliary microbiota. The risk factors of common bile duct calculi were analyzed numerically combined with the pressure in the sphincter of Oddi. Different biliary microbiota were found in all cases. Patients with sphincter of Oddi dysfunction had significantly increased biliary microbiota as well as significantly higher level of systemic inflammation than patients with normal sphincter of Oddi. The systemic inflammatory response of patients with sphincter of Oddi dysfunction is more severe, and their microbial community significantly differs from that of patients with normal sphincter of Oddi, which makes biliary tract infection more likely; furthermore, the biliary tract of patients with sphincter of Oddi dysfunction has more gallstone-related bacterial communities.

Prognostic Nutritional Index (PNI) and Neutrophil to Lymphocyte Ratio (NLR) as Predictors of Short-Term Survival in Patients with Advanced Malignant Biliary Obstruction Treated with Percutaneous Transhepatic Biliary Drainage

Effective biliary tree decompression plays a central role in the palliation of malignant biliary obstruction (MBO). When endoscopic drainage is unfeasible or unsuccessful, percutaneous transhepatic biliary drainage (PTBD) is the method of choice and preferred treatment approach in advanced hilar MBO. The prognostic nutritional index (PNI) reflects the patient's immunonutritional status, while the neutrophil to lymphocyte ratio (NLR) reflects the patient's inflammation status. The aim of the present study was to evaluate the prognostic value of preprocedural PNI and NLR on short-term survival in the advanced stage MBO population threatened with PTBD and to characterize the differences in immunonutritional and inflammatory status between 60-day survivors and non-survivors, as well as analyze other variables influencing short-term survival. This single-center retrospective study was conducted on patients undergoing palliative PTBD caused by MBO as a definitive therapeutic treatment between March 2020 and February 2022. After the procedure, patients were followed until the end of August 2022. A total of 136 patients with malignant biliary obstruction were included in the study. Based on receiver operating characteristic (ROC) curve analysis, optimal cut off-values for NLR (3) and PNI (36.7) were determined. In univariate regression analysis, age, absolute neutrophil count, albumin level, NLR ≤ 3, and PNI ≥ 36.7 were significant predictors of 60-day survival. Level of obstruction and PNI ≥ 36.7 were statistically significant independent predictors of 60-day survival in a multivariate regression model. Using PNI ≥ 36.7 as a significant coefficient from the multivariate regression model with the addition of NLR ≤ 3 from univariate analysis, a 60-day survival score was developed. PNI and NLR are easy to calculate from routine blood analysis, which is regularly conducted for cancer patients. As such, they represent easily available, highly reproducible, and inexpensive tests capable of expressing the severity of systemic inflammatory responses in patients with cancer. Our study highlights that preprocedural PNI and NLR values provide predictors of short-term survival in patients with MBO treated with palliative PTBD. In addition, the proposed 60-day survival score can contribute to better selection of future candidates for PTBD and recognition of high-risk patients with expected poor outcomes.

Systemic Inflammation Is Implicated in De Novo Seizures Following Meningioma Resection

Abstract AIMS To investigate the association between perioperative peripheral blood inflammatory markers and seizures in patients who have undergone meningioma resection. METHOD A single neurosurgery tertiary centre blood bank database was screened to extract pre-operative and post-operative white cell count (WCC), neutrophils, lymphocytes, monocytes, platelets and neutrophil-lymphocyte ratio (NLR) and derived NLR (dNLR). All patients who underwent resection of meningioma from 2012 to 2020 were eligible. Patients were excluded if they had an inflammatory condition, peri-operative infection, medical illness or operative complication. RESULTS 30 patients suffered pre-operative seizures only, 16 experienced de novo post-operative seizures within 1 year and 42 patients did not experience seizures throughout their treatment timeline. In those who had never had a seizure, there was a significant increase in WCC post-operatively (15.2 vs. 10.6 × 109/L (95% CI 2.1-8.2), p=0.02). Patients who suffered de novo seizures had a significantly higher post-operative day 1 to 4 WCC than those with no seizures (21.1 vs. 14.8 × 109/L (2.1-12.6), p=0.48). However, this difference of WCC was poorly predictive of de novo seizures at one year (AUC 0.61). There was no difference in pre-operative inflammatory markers between pre-operative seizure patients, de novo seizure or never seizure patients. CONCLUSION There is a significantly higher post-operative systemic inflammatory response in patients who suffered de novoseizures after meningioma resection. Peripheral blood markers have the potential to predict seizures in patients with meningioma.

ASO Author Reflections: Evaluation of the Longitudinal Changes in the Systemic Inflammatory Response of Patients With Hepatocellular Carcinoma.

ASO Author Reflections: Evaluation of the Longitudinal Changes in the Systemic Inflammatory Response of Patients With Hepatocellular Carcinoma.

Inflammasome Activation: A Keystone of Proinflammatory Response in Obstructive Sleep Apnea

Introduction: As the mechanism that links obstructive sleep apnea (OSA) with the regulation of inflammatory response is not well known, it is important to understand the inflammasome activation, mainly of NLRP3 (nucleotide-binding oligomerization domain-like receptor 3).To assess the NLRP3 activity in patients with severe OSA and to identify its role in the systemic inflammatory response of patients with OSA. Materials and Methods: We analyzed the NLRP3 activity as well as key components of the inflammasome cascade, such as adaptor molecule apoptosis-associated speck-like protein, caspase-1, Gasdermin D, IL-1b, IL-18, and tissue factor, in monocytes and plasma from patients with severe OSA and control subjects without sleep apnea. We explored the association of the different key markers with inflammatory comorbidities. Results: Monocytes from patients with severe OSA presented higher NLRP3 activity than those from control subjects, which directly correlated with the apnea–hypopnea index and hypoxemic indices. NLRP3 overactivity triggered inflammatory cytokines (Il-1b and IL-18) via caspase-1 and increased Gasdermin D, allowing for tissue factor to be released. In vitro models confirmed that monocytes increase NLRP3 signaling under intermittent hypoxia in a hypoxia- inducible factor-1a–dependent manner, and/or in combination with plasma from patients with OSA. Plasma concentrations of tissue factor were higher in patients with OSA with systemic inflammatory comorbidities than in those without them. Conclusions: In patients with severe OSA, NLRP3 activation might be a linking mechanism between intermittent hypoxia and other OSA-induced immediate changes with the development of systemic inflammatory response.

Age modifies both the maximal temperature and inflammatory response in patients with SARS-CoV-2 infection

To determine the maximal response of the temperature and inflammatory response to SARS-CoV-2 infection and how these are modified by age. Participants were patients admitted to hospital with SARS-CoV-2 infection. For each participant, the maximal temperature and serum C-reactive protein (CRP) were identified and stratified by age. In a secondary analysis, these were compared in patients treated before and after dexamethasone. Mean maximal temperature varied by age (p<0.001; ANOVA) with the highest mean maximal temperature of 37.3°C observed in patients aged 30-49 years and decreasing maximal mean temperatures in the older age groups, with the lowest measure of 36.8°C observed in individuals aged 90-99 years. The mean maximal serum CRP also varied across age groups (p<0.001; ANOVA) and increased with age across all age categories from 34.5 mg/dL (95% confidence interval (CI) 22.0-47.0) for individuals aged 20-29 years to 77.6 mg/dL (95% CI 72.0-83.2) in those aged 80-89 years. After dexamethasone became standard treatment for COVID-19 pneumonia, mean maximal CRP decreased by 17 mg/dL (95% CI -22 to -11). Age modifies both maximal temperature and systemic inflammatory response in patients with SARS-CoV-2 infection.

Inflammasome Activation: A Keystone of Proinflammatory Response in Obstructive Sleep Apnea.

Rationale: As the mechanism that links obstructive sleep apnea (OSA) with the regulation of inflammatory response is not well known, it is important to understand the inflammasome activation, mainly of NLRP3 (nucleotide-binding oligomerization domain-like receptor 3). Objectives: To assess the NLRP3 activity in patients with severe OSA and to identify its role in the systemic inflammatory response of patients with OSA. Methods: We analyzed the NLRP3 activity as well as key components of the inflammasome cascade, such as adaptor molecule apoptosis-associated speck-like protein, caspase-1, Gasdermin D, IL-1β, IL-18, and tissue factor, in monocytes and plasma from patients with severe OSA and control subjects without sleep apnea. We explored the association of the different key markers with inflammatory comorbidities. Measurements and Main Results: Monocytes from patients with severe OSA presented higher NLRP3 activity than those from control subjects, which directly correlated with the apnea-hypopnea index and hypoxemic indices. NLRP3 overactivity triggered inflammatory cytokines (IL-1β and IL-18) via caspase-1 and increased Gasdermin D, allowing for tissue factor to be released. In vitro models confirmed that monocytes increase NLRP3 signaling under intermittent hypoxia in a hypoxia-inducible factor-1α-dependent manner, and/or in combination with plasma from patients with OSA. Plasma concentrations of tissue factor were higher in patients with OSA with systemic inflammatory comorbidities than in those without them. Conclusions: In patients with severe OSA, NLRP3 activation might be a linking mechanism between intermittent hypoxia and other OSA-induced immediate changes with the development of systemic inflammatory response.

Chronic Endotoxemia and Peculiarities of Systemic Inflammatory Response in Patients with Osteoarthrosis Requiring Primary Arthroplasty of Large Joints

INTRODUCTION: Infectious complications after the primary arthroplasty of large joints in patients with end-stage osteoarthrosis are often associated with self-opportunistic pathogenic microflora in cases of compromised immune response and systemic inflammatory reactions. Thus, the associated pathogenic mechanisms require additional study.&#x0D; AIM: To examine the peculiarities of signs of endotoxemia and the severity of the systemic inflammatory response (SIR) in patients with osteoarthritis of large joints requiring primary arthroplasty.&#x0D; MATERIALS AND METHODS: A total of 110 patients (67 women, 43 men, average age 49.2 years, age range 41.152.8 years) with stage IIIIV primary osteoarthrosis of the knee joints and 30 healthy individuals (control group) (15 men, 15 women, average age 49.4 years, age range 37.253.1 years) were examined. Analyses were carried out on blood serum concentrations of the endotoxemia parameter lipopolysaccharide (LPS), acute-phase proteins (C-reactive protein [CRP]), lipopolysaccharide-binding protein (LBP), and markers of the proinflammatory activity of cytokine regulation system (interleukine-1 [Il-1]) and activation of cell-mediated immunity (neopterin). Correlation relationships between the studied parameters were evaluated depending on the severity of the SIR.&#x0D; RESULTS: Forty patients were identified (28 women, 12 men) to have signs of high inflammatory activity (CRP concentration 7.59 g/L and erythrocyte sedimentation rate 10 mm/h) and evident synovitis based on the ultrasound data of the joint. The parameters in this group were analyzed: LPS, 12.08 (10.77; 12.65) ng/mL; LBP, 26.31 (25.48; 27. 11) g/mL; Il-1, 8.4 (7.3; 8.7) pg/mL; and neopterin, 9.36 (8.58; 9.62) pg/mL. These values significantly (р 0.05, KruskalWallis test) exceeded the values in the moderate SIR activity and control groups. Correlation analysis (Spearman r-test) in patients with signs of enhanced inflammatory activity revealed a moderate positive relationship between LPS and CRP concentrations, and reduction of positive relationships between LPS and Il-1 and in LPS and LBP.&#x0D; CONCLUSION: Impaired SIR with the underlying excessive proinflammatory activity of the cytokine regulation system, activation of the cell-mediated immunity, and systemic endotoxemia in patients with end-stage osteoarthrosis of large joints requires additional preoperative and postoperative monitoring. The results substantiate the necessity of a detailed investigation of endotoxemia as a probable component of the pathogenesis and sanogenesis of complications following the primary arthroplasty of large joints.

Prognostic impact of postoperative systemic inflammatory response in patients with stage II/III gastric cancer

This study examined whether the systemic inflammatory response present in the early phase of the postoperative state correlates with long-term outcomes and to identify markers in patients with stage II/III gastric cancer. 444 consecutive patients who underwent radical gastrectomy for stage II/III gastric cancer were retrospectively reviewed. We evaluated maximum serum C-reactive protein (CRPmax) and white blood cell count (WBCmax), defined as the maximum serum CRP level and maximum WBC count during the interval from surgery until discharge, as systemic inflammation markers. In univariate analyses, CRPmax, WBCmax and infectious complications were significantly associated with both overall survival (OS) (p < 0.001, p < 0.001 and p = 0.011, respectively) and relapse-free survival (RFS) (p < 0.001, p = 0.001 and p < 0.001, respectively). Multivariate analysis revealed that high-CRPmax (> 9.2 mg/dL) was an independent prognostic factor for OS (hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.19–2.36, p = 0.003) and RFS (HR 1.56, 95% CI 1.12–2.18, p = 0.009), while WBCmax and infectious complications were not. CRPmax, which reflects the magnitude of systemic inflammation induced by surgical stress and postoperative complications in the early phase after surgery, may be a promising prognostic indicator in patients with stage II/III gastric cancer who undergo curative resection.

Diagnostic levels of sepsis biomarkers in children with oncological diseases.

The data on the diagnostic levels of sepsis markers in blood plasma in 117 patients with oncological diseases at the age from 1 to 18 years are presented. The patients were divided into 4 groups depending on the outcome of the clinical course of the inflammatory process or infectious complications: group 1 - patients with no complications of anticancer treatment (n = 13/11.1%), group 2 - the presence of a systemic inflammatory response in patients (n = 64/54.7%), group 3 - patients with sepsis (n = 27/23.1%), group 4 - patients with septic shock (n = 13/11.1%). The threshold level of presepsin between groups 1 and 2 was 202 pg/ml, 371 pg/ml between groups 1 and 3, 604 pg/ml between groups 2 and 3 and 1500 pg/ml between groups 3 and 4. For procalcitonin, the threshold level between groups 1and 2 was 0.23 ng/ml, 0.48 ng/ml between groups 1 and 3, 0.51 ng/ml between groups 2 and 3 and 3.9 ng/ml between groups 3 and 4. The threshold value of C-reactive protein in patients with solid tumors was 12.6 g/l between groups 1 and 2. In patients with oncohematological diseases, the threshold level of C-reactive protein was 43.4 g / L between groups 2 and 3, 77.1 g / L between groups 2 and 4. According to the ROC analysis, presepsin was superior to procalcitonin and C-reactive protein in the diagnosis of septic complications.