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Obstructive sleep apnea (OSA) syndrome is a prevalent form of respiratory sleep disorder, with an increasing prevalence among children. The consequences of OSA include obesity, diabetes, cardiovascular disease, and neuropsychological diseases. Despite its pervasive impact, a significant proportion of individuals especially children remain unaware that they suffer from OSA. Consequently, there is an urgent need for an accessible diagnostic approach. In this study, we conducted a bioinformatic analysis to identify potential biomarkers from a proteomics dataset comprising serum samples from children with OSA in the progression stage. In the Gene Set Enrichment Analysis (GSEA), we observed that the complement and immune response pathways persisted throughout the development of OSA and could be detected in the early stages. Subsequent to soft clustering and WGCNA analysis, it was revealed that the Hippo pathway, including ITGAL and FERMT3, plays a role in mild OSA. The analysis revealed a significant alteration of the complement and coagulation pathways, including TFPI and MLB2, in moderate OSA. In severe OSA, there was an association between hypoxia and the extracellular matrix (ECM) receptor interaction and collagen binding. In summary, it can be posited that the systemic inflammation may persist throughout the progression of OSA. Furthermore, severe OSA is characterized by abnormal vascular endothelial function, which may be attributed to chronic hypoxia. Finally, four potential biomarkers (ITGAL, TFPI, TTR, ANTXR1) were identified based on LASSO regression, and a prediction model for OSA progression was constructed based on the biomarkers. [ABSTRACT FROM AUTHOR]

Background: Beyond being a pulmonary disease, chronic obstructive pulmonary disease (COPD) presents with extrapulmonary manifestations including reduced cognitive, cardiovascular, and muscle function. While exercise training is the cornerstone in the non-pharmacological treatment of COPD, there is a need for new exercise training methods due to suboptimal adaptations when following traditional exercise guidelines, often applying moderate-intensity continuous training (MICT). In people with COPD, short-duration high-intensity interval training (HIIT) holds the potential to induce a more optimal stimulus for training adaptations while circumventing the ventilatory burden often associated with MICT in people with COPD. We aim to determine the effects of supramaximal HIIT and MICT on extrapulmonary manifestations in people with COPD compared to matched healthy controls. Methods: COPD-HIIT is a prospective, multi-centre, randomized, controlled trial with blinded assessors and data analysts, employing a parallel-group designed trial. In phase 1, we will investigate the effects and mechanisms of a 12-week intervention of supramaximal HIIT compared to MICT in people with COPD (n = 92) and matched healthy controls (n = 70). Participants will perform watt-based cycling two to three times weekly. In phase 2, we will determine how exercise training and inflammation impact the trajectories of neurodegeneration, in people with COPD, over 24 months. In addition to the 92 participants with COPD performing HIIT or MICT, a usual care group (n = 46) is included in phase 2. In both phases, the primary outcomes are a change from baseline in cognitive function, cardiorespiratory fitness, and muscle power. Key secondary outcomes include change from baseline exercise tolerance, brain structure, and function measured by MRI, neuroinflammation measured by PET/CT, systemic inflammation, and intramuscular adaptations. Feasibility of the interventions will be comprehensively investigated. Discussion: The COPD-HIIT trial will determine the effects of supramaximal HIIT compared to MICT in people with COPD and healthy controls. We will provide evidence for a novel exercise modality that might overcome the barriers associated with MICT in people with COPD. We will also shed light on the impact of exercise at different intensities to reduce neurodegeneration. The goal of the COPD-HIIT trial is to improve the treatment of extrapulmonary manifestations of the disease. Trial registration: Clinicaltrials.gov: NCT06068322. Prospectively registered on 2023-09-28. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF) is suggested to be influenced by inflammation. Leukocyte indices, including the neutrophil–lymphocyte ratio (NLR), the monocyte–lymphocyte ratio (MLR), and the pan-immune inflammation value (PIV), can be utilized as biomarkers of systemic inflammation. Their prognostic utility is yet to be fully understood. Methods: Between December 2010 and May 2023, patients presenting to a tertiary referral center for HFpEF were included into a prospective registry. The association of the NLR, MLR, and PIV with the composite endpoint of all-cause mortality and HF-related hospitalization was tested utilizing Cox regression analysis. Results: In total, 479 patients (median 74.3, interquartile range (IQR): 69.22–78.3 years, 27.8% male) were included. Patients were observed for 43 (IQR: 11–70) months, during which a total of 267 (55.7%) patients met the primary endpoint. In a univariate Cox regression analysis, an above-the-median NLR implied a hazard ratio (HR) of 1.76 (95%-confidence interval (CI): 1.38–2.24, p < 0.001), an MLR of 1.46 (95%-CI: 1.14–1.86, p = 0.003), and a PIV of 1.67, 95%-CI: 1.30–2.13, p < 0.001) for the composite endpoint. After adjustment in a step-wise model, the NLR (HR: 1.81, 95%-CI: 1.22–2.69, p = 0.003), the MLR (HR: 1.57, 95%-CI: 1.06–2.34, p = 0.026), and the PIV (HR: 1.64, 95%-CI: 1.10–2.46, p = 0.015) remained significantly associated with the combined endpoint. Conclusions: The NLR, the MLR, and the PIV are simple biomarkers independently associated with outcomes in patients with HFpEF. [ABSTRACT FROM AUTHOR]

The presence of Fusobacterium nucleatum is associated with an immunosuppressive tumor immune microenvironment (TIM) in primary colorectal cancer (CRC), contributing to tumor progression. Its persistence in CRC liver metastasis tissues raises questions about its role in modulating local and systemic immune responses and influencing recurrence patterns. This retrospective cohort study of 218 patients with CRC liver metastasis investigated the association of F. nucleatum in CRC liver metastasis tissues with systemic inflammation, TIM alterations, and the number of metastatic organs involved in recurrence. Two‐step polymerase chain reaction (PCR), including digital PCR, detected F. nucleatum in 42% (92/218) of fresh‐frozen specimens of CRC liver metastases. Compared with the F. nucleatum‐none group, the F. nucleatum‐high group showed higher C‐reactive protein levels (0.82 vs. 0.22 mg/dL; Ptrend = 0.02), lower numbers of CD8+ cells (33.2 vs. 65.3 cells/mm2; Ptrend = 0.04) and FOXP3+ cells (11.3 vs. 21.7 cells/mm2; Ptrend = 0.01) in the TIM, and a greater number of metastatic organs involved in recurrence (1.6 vs. 1.1; p < 0.001). The presence of F. nucleatum in CRC liver metastasis tissues was associated with increased systemic inflammation, TIM alterations, and a greater number of metastatic organs involved in recurrence. These findings suggest a potential contribution of F. nucleatum to the metastatic propensity of CRC cells and could inform future research to enhance understanding of the interaction between tumor, host, and microbes in the metastatic process. [ABSTRACT FROM AUTHOR]

Systemic inflammation and immunodeficiency are important components of cirrhosis-associated immune dysfunction (CAID), the severity of which is dynamic, progressive, and associated with the greater deterioration of liver function. Two inflammation phenotypes have been described: low-grade and high-grade systemic inflammation. Both of these phenotypes are related to liver cirrhosis function; thus, high-grade inflammation is correlated with the severity of hepatic insufficiency, bacterial translocation, and organic insufficiency, with which the risk of infections increases and the prognosis worsens. Bacterial translocation (BT) plays a relevant role in persistent systemic inflammation in patients with cirrhosis, and the prophylactic employment of antibiotics is useful for reducing events of infection and mortality. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD), usually caused by long-term tobacco smoking, is independently associated with systemic inflammation. However, little is known about the systemic inflammatory status of patients with early-stage COPD (classified as GOLD 1) and long-term smokers with normal lung function (LF). Here, we characterised the early changes in the associated inflammatory state in patients with GOLD 1 and in long-term smokers with normal LF. Methods: Fresh blood samples from 27 patients with GOLD 1, 27 long-term smokers and 14 non-smokers were analysed. Results: Ex vivo blood analysis revealed greater leucocyte-platelet adhesion to TNFα-stimulated pulmonary endothelium in patients with GOLD 1 than in smokers and non-smokers. In addition, platelet reactivity (platelet count and activation, and fibrinogen levels) and the frequency of leucocyte-platelet aggregates were higher in the GOLD 1 group than in the other groups. Some of these findings correlated with the severity of lung dysfunction, while platelet hyperactivity correlated positively with leucocyte-platelet adhesion. The GOLD 1 group also had a higher Th17/Treg ratio and higher circulating levels of IL-17C and C-reactive protein than the other groups. However, long-term smokers also had higher leucocyte counts and activation, and higher plasma levels of TNFα and IL-6 than non-smokers. Conclusion: Our data suggest that the altered inflammatory parameters in longterm smokers may represent early biomarkers of COPD. Accordingly, peripheral immune monitoring based on the above parameters may be useful to prevent disease progression in long-term smokers with normal LF and early COPD. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores whether Escherichia coli carrying the polyketide synthetase (pks) gene cluster in colorectal cancer (CRC) liver metastasis tissues influence immune responses and cancer recurrence patterns. Analyzing tissues from 239 patients, we found that pks+ E. coli was present in 66.7% of liver metastasis cases. Higher levels of pks+ E. coli were associated with lower levels of the serum C-reactive protein, fewer densities of CD4+ cells and CD163+ cells in the tumor microenvironment, and a reduction in the number of organs affected by recurrent metastasis. These findings suggest that pks+ E. coli may influence both systemic and local immune responses, potentially reducing the diversity of affected metastatic organs. Colibactin, a genotoxin produced by Escherichia coli strains harboring the polyketide synthetase (pks) gene cluster, causes DNA damage and somatic mutations. pks+ E. coli is enriched in primary colorectal cancer (CRC) and is associated with clonal driver mutations, but its role in CRC liver metastasis is unclear. We assessed the association of pks+ E. coli in CRC liver metastasis tissues with systemic and local immune responses and the number of organs involved in recurrence using specimens and clinicopathological data from 239 patients with CRC liver metastasis who underwent metastasectomy. The levels of pks+ E. coli in fresh-frozen specimens were quantified as "very low" (<50th percentile), "low" (50th to 75th percentiles), and "high" (>75th percentile) using a digital PCR. Immunohistochemical analysis of tumor-infiltrating immune cells was performed using tissue microarrays. Systemic inflammation was evaluated using serum C-reactive protein (CRP) levels. pks+ E. coli was detected in 66.7% (157 of 239) liver metastasis tissues. Higher levels of pks+E. coli were associated with decreased serum CRP levels and reduced densities of CD4+ cells and CD163+ cells in the tumor-immune microenvironment. The "high" pks+ E. coli group had fewer metastatic organs involved than the "very low" pks+ E. coli group (mean number of organs: 1.00 vs. 1.23). These findings suggest that pks+ E. coli play a modulating role in CRC metastasis. [ABSTRACT FROM AUTHOR]

Background: There is no consensus on the cause and effect of systemic chronic inflammation (SCI) regarding chronic obstructive pulmonary disease (COPD). The impact of second-hand smoke (SHS) on COPD has reached inconsistent conclusions. Methods: The China Kadoorie Biobank cohort was followed up from the 2004–08 baseline survey to 31 December 2018. Among the selected 445,523 participants in the final analysis, Cox and linear regressions were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of tobacco exposure with COPD risk and baseline levels of log-transformed inflammatory factors [βs (95% CIs)], respectively. Results: Participants were followed up for a median of 12.1 years and 11,825 incident COPD events were documented. Ever-smokers were associated with a higher risk of COPD than non-smokers with non-weekly SHS exposure. A younger age to start smoking, a greater amount of daily tobacco consumption, and deeper inhalation were associated with increased risk of COPD and correlated with elevated levels of plasma high-sensitivity C-reactive protein (hs-CRP, all Ptrend < 0.001) even two years before COPD onset. Among former smokers, COPD risk declined with longer smoking cessation (Ptrend < 0.001) and those quitting smoking for over ten years presented no difference in COPD risk and hs-CRP level from non-smokers [HR (95% CI) = 1.05 (0.89, 1.25), β (95% CI) = 0.17 (− 0.09, 0.43)]. Among non-smokers, weekly SHS exposure was associated with a slightly higher COPD risk [HR (95% CI) = 1.06 (1.01, 1.12)]. Conclusions: Incremental exposure to tobacco smoke was related to elevated SCI level before COPD onset, then an increase in COPD susceptibility. Quitting smoking as early as possible is suggested as a practical approach to reducing COPD risk in smokers. Given the high prevalence of both COPD and SHS exposure, the risk associated with SHS exposure deserves attention. [ABSTRACT FROM AUTHOR]

PURPOSE Systemic inflammation and body composition are associated with survival outcomes of cancer patients. This study aimed to examine the combined prognostic value of systemic inflammatory markers and body composition parameters in patients with locally advanced cervical cancer (LACC). METHODS Patients who underwent concurrent chemoradiotherapy (CCRT) for LACC at a tertiary referral teaching hospital between January 2010 and January 2018 were enrolled. A predictive model was established based on systemic immune-inflammation index (SII) and computer tomography-derived visceral fat-to-muscle ratio (vFMR). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan--Meier method and Cox regression models. The model performance was assessed using discrimination, calibration, and clinical usefulness. RESULTS In total, 212 patients were enrolled. The SII and vFMR were closely related, and both independently predicted survival (P < 0.05). A predictive model was established based on the above biomarkers and included three subgroups: high-risk [both high SII (>828) and high vFMR (>1.1)], middle-risk (either high SII or high vFMR), and low-risk (neither high SII nor high vFMR). The 3-year OS (PFS) rates for low-, middle-, and high-risk patients were 90.5% (86.0%), 73.9% (58.4%), and 46.8% (36.1%), respectively (P < 0.05). This model demonstrated satisfactory predictive accuracy (area under the curve values for predicting 3-year OS and PFS were 0.704 and 0.718, respectively), good fit (Hosmer--Lemeshow tests: P > 0.05), and clinical usefulness. CONCLUSION Systemic inflammatory markers combined with body composition parameters could independently predict the prognosis of patients with LACC, highlighting the utilization of commonly collected indicators in decision-making processes. CLINICAL SIGNIFICANCE The SII and vFMR, as well as their composite indices, were promising prognostic factors in patients with LACC who received definitive CCRT. Future studies are needed to explore novel therapies to improve the outcomes in high-risk patients. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by irreversible progressive airflow limitation, often manifested by persistent cough, sputum production and other respiratory symptoms that pose a serious threat to human health and affect the quality of life of patients. The disease is associated with chronic inflammation, which is associated with the onset and progression of COPD, but anti-inflammatory therapy is not first-line treatment. Inflammation has multiple manifestations and phenotypes, and this heterogeneity reveals different patterns of inflammation, making treatment difficult. This paper aims to explore the direction of more effective antiinflammatory treatment by analyzing the nature of inflammation and the molecular mechanism of disease occurrence and development in COPD patients, and to provide new ideas for the treatment of COPD patients. [ABSTRACT FROM AUTHOR]

Streptococcus suis causes diseases in pigs and has emerged as a zoonotic agent. When infected, the host develops an exacerbated inflammation that can lead to septic shock and meningitis. Although neutrophils greatly infiltrate the lesions, their dynamics during S. suis infection remain poorly described. Moreover, very few studies reported on the production and role of a key factor in the regulation of neutrophils: the colony-stimulating granulocyte factor (G-CSF). In this study, we characterized the G-CSF-neutrophil axis in the pathogenesis of S. suis induced disease. Using a mouse model of S. suis infection, we first evaluated the recruitment of neutrophils and their activation profile by flow cytometry. We found that infection provokes a massive neutrophil recruitment from the bone marrow to the blood and spleen. In both compartments, neutrophils displayed multiple activation markers. In parallel, we observed high systemic levels of G-CSF, with a peak of production coinciding with that of neutrophil recruitment. We then neutralized the effects of G-CSF and highlighted its role in the release of neutrophils from the bone marrow to the blood. However, it did not affect bacteremia nor the cytokine storm induced by S. suis. In conclusion, systemic GCSF induces the release of neutrophils from the bone marrow to the blood, but its role in inflammation or bacterial clearance seems to be compensated by unknown factors. A better understanding of the role of neutrophils and inflammatory mediators could lead to better strategies for controlling the infection caused by S. suis. [ABSTRACT FROM AUTHOR]

Children with obstructive sleep apnea (OSA) frequently experience chronic low-grade systemic inflammation, with the inflammasome playing a central role in OSA. This cross-sectional study evaluated the relationship between weight status, autonomic function, and systemic inflammation in a cohort of 55 children with OSA, predominantly boys (78%) with an average age of 7.4 ± 2.2 years and an apnea-hypopnea index of 14.12 ± 17.05 events/hour. Measurements were taken of body mass index (BMI), sleep heart-rate variability, morning circulatory levels of interleukin-1β, interleukin-1 receptor antagonist, and interleukin-6, and tumor necrosis factor-α, anthropometry, and polysomnography. Multiple linear regression modeling showed that an apnea-hypopnea index was significantly associated with BMI, the standard deviation of successive differences between normal-to-normal intervals during N3 sleep, and the proportion of normal-to-normal interval pairs differing by more than 50 ms during rapid-eye-movement sleep. A moderated mediation model revealed that interleukin-1 receptor antagonist levels mediated the association between BMI and interleukin-6 levels, with sympathovagal balance during N3 sleep and minimum blood oxygen saturation further moderating these relationships. This study highlights the complex relationships between BMI, polysomnographic parameters, sleep heart-rate-variability metrics, and inflammatory markers in children with OSA, underlining the importance of weight management in this context. [ABSTRACT FROM AUTHOR]

Patients affected by chronic kidney disease (CKD) are generally considered to be frailer than those with preserved renal function. We cross-sectionally evaluated the associations between frailty, malnutrition–inflammation syndrome and circulating inflammatory cytokines in 115 older individuals with advanced CKD. As for frailty definition, we adopted Fried's frailty phenotype (FP), while malnutrition–inflammation syndrome was assessed using the Malnutrition–Inflammation Score (MIS) and circulating inflammatory cytokines (IL-6; TNFα; MCP-1). A total of 48 patients were frail, and mean eGFR was comparable in both frail and non-frail patients (24 ± 10 vs. 25 ± 11 mL/min/1.73 m2; p = 0.63). Frail patients had higher MIS (6 [4–11] vs. 4 [3–5]; p < 0.0001) but cytokine concentrations were comparable in both groups. At multivariate regression, FP was independently associated with MIS, age, gender and pre-albumin but not with cytokines. However, we found some associations between inflammatory cytokines and some specific frailty criteria: weight loss and slowness were associated with MCP-1 (respectively p = 0.049 and p < 0.0001) and weakness with IL-6 (p = 0.005); in conclusion, in older patients with advanced CKD, frailty is strictly associated with malnutrition–inflammation syndrome but not with circulating inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Introduction: Stroke, a leading cause of death and disability worldwide, is primarily ischemic and linked to hypertension. Hypertension, characterized by systemic chronic inflammation, significantly increases stroke risk. This study explores the association of novel systemic inflammatory markers (SII, PIV, SIRI) with stroke prevalence in hypertensive U.S. adults using NHANES data. Methods: We analyzed data from hypertensive participants in the NHANES 1999-2020 survey, excluding those under 20, pregnant, or with missing data, resulting in 18,360 subjects. Systemic inflammatory markers (SII, PIV, SIRI) were calculated from blood counts. Hypertension and stroke status were determined by self-report and clinical measurements. Covariates included sociodemographic, lifestyle, and medical history factors. Weighted statistical analyses and multivariate logistic regression models were used to explore associations, with adjustments for various covariates. Ethical approval was obtained from the NCHS Ethics Review Board. Results: In a cohort of 18,360 hypertensive individuals (mean age 56.652  years), 7.25% had a stroke. Stroke patients were older, had lower PIR, and were more likely to be female, single, less educated, smokers, non-drinkers, physically inactive, and have diabetes and CHD. Multivariate logistic regression showed that SII was not significantly associated with stroke. However, PIV and SIRI were positively associated with stroke prevalence. Each unit increase in lnPIV increased stroke odds by 14% (OR = 1.140, p = 0.0022), and lnSIRI by 20.6% (OR = 1.206, p = 0.0144). RCS analyses confirmed J-shaped associations for lnPIV and lnSIRI with stroke. Stratified analyses identified gender and smoking as significant effect modifiers. Smoking was significantly associated with elevated PIV, SIRI, and SII levels, especially in current smokers. Conclusion: Elevated PIV and SIRI levels significantly increase stroke prevalence in hypertensive individuals, notably among males and smokers. A predictive model with PIV, SIRI, and sociodemographic factors offers strong clinical utility. [ABSTRACT FROM AUTHOR]

Aims: We hypothesized that the current gold standard for risk stratification of patients with acute heart failure (AHF), the Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF (MEESSI‐AHF) risk score, can be further improved by adding systemic inflammation as quantified by C‐reactive protein (CRP). Methods and results: In a prospective multicentre diagnostic study (BASEL V), AHF was centrally adjudicated by two independent cardiologists. The MEESSI‐AHF risk score was calculated using an established reduced and recalibrated model containing 12 independent risk factors. Model extension was performed by refitting and adding CRP in the logistic regression model with 30‐day mortality as binary outcome. Discrimination, calibration and clinical usefulness were used to assess the performance of the extended Multiple Estimation of risk based on the Emergency department Spanish Score In patients (MEESSI) model. Validation was performed in an independent, retrospective and single‐centre AHF cohort. Among 1208 AHF patients with complete data allowing calculation of the recalibrated MEESSI and the extended MEESSI models, the prognostic accuracy for 30‐day mortality of the extended MEESSI model (c‐statistic 0.83, 95% confidence interval [CI] 0.79–0.87) was significantly higher compared to the recalibrated model (c‐statistic 0.79, 95% CI 0.75–0.83, p = 0.013). The extended model allowed to stratify a higher percentage of patients into the lowest risk group compared to the recalibrated model (33.1% vs. 20.3%). Demonstrating a calibration plot's slope of 1.00 (95% CI 0.81–1.19) and an intercept of 0.0 (95% CI −0.22 to 0.22), the extended MEESSI model achieved excellent and improved calibration. Results were confirmed in the independent validation cohort (n = 575). Conclusions: Quantifying inflammation using CRP concentration provided incremental value in AHF risk stratification using the established MEESSI model. [ABSTRACT FROM AUTHOR]

Background: Spontaneous intracerebral hemorrhage (ICH) is one of the leading causes of mortality in intensive care units. The role of systemic hyperintense inflammation (SHI) in the pathogenesis of critical complications of ICH remains a poorly understood problem. There is a specific variant of severe ICH associated with increased intracranial pressure and occlusion of intracranial vessels, defined as ineffective cerebral blood flow (IECBF). Methods: To evaluate the role of SHI in the pathogenesis of severe (comatose) ICH in a dynamic comparison of patients with IECBF (n-26) and without IECBF (n-52). The SHI integral score criterion (SI scale) was used, including certain values of plasma concentrations of IL-6, IL-8, IL-10; TNF-α, PCT, cortisol, myoglobin, troponin I, D-dimer, and, additionally, SOFA scale values. Blood levels of ACTH and neuron-specific enolase (NSE) were also assessed. Results: Twenty-eight-day mortality in severe ICH reached 84.6% (without IECBF) and 96.2% (with IECBF). Clear signs of SHI were detected in 61.5%/87.8% (without IECBF) and 0.0%/8.7% (with IECBF) within 1–3/5–8 days from the onset of ICH manifestation. The lower probability of developing SHI in the IECBF group was associated with low blood NSE concentrations. Conclusions: The development of SHI in ICH is pathogenetically related to the permeability of the blood–brain barrier for tissue breakdown products and other neuroinflammatory factors. [ABSTRACT FROM AUTHOR]

The severity and invasiveness of clinical outcomes from organic responses to trauma are influenced by individual, surgical, and anesthetic factors. A stress response elicits neuroendocrine and immune reactions that may lead to multi-organ dysfunction. The degree of neuroinflammatory reflex activation from trauma can increase pro-inflammatory cytokine production, leading to endothelial dysfunction, glycocalyx damage, neutrophil activation, and multisystem tissue destruction. A shift in patient treatment towards a neuroinflammatory perspective has prompted a new evaluation protocol for surgical patients, required to understand surgical pathogenesis and its link to chosen anesthetic–surgical methods. The goal of this study is to summarize and disseminate the present knowledge about the mechanisms involved in immune and neuroendocrine responses, focusing on video laparoscopic surgeries. This article outlines various measures cited in the literature aimed at reducing the burden of surgical trauma. It reviews anesthetic drugs, anesthetic techniques, and intensive care procedures that are known to have immunomodulatory effects. The results show a preference for more sensitive inflammatory mediators to tissue trauma serving as care tools, indicators for prognosis, and therapeutic outcomes. [ABSTRACT FROM AUTHOR]

The respiratory microbiome may influence the development and progression of COPD by modulating local immune and inflammatory events. We aimed to investigate whether relative changes in respiratory bacterial abundance are also associated with systemic inflammation, and explore their relationship with the main clinical COPD phenotypes. Multiplex analysis of inflammatory markers and transcript eosinophil-related markers were analyzed on peripheral blood in a cohort of stable COPD patients (n = 72). Respiratory microbiome composition was analyzed by 16S rRNA microbial sequencing on spontaneous sputum. Spearman correlations were applied to test the relationship between the microbiome composition and systemic inflammation. The concentration of the plasma IL-8 showed an inverted correlation with the relative abundance of 17 bacterial genera in the whole COPD cohort. COPD patients categorized as eosinophilic showed positive relationships with blood eosinophil markers and inversely correlated with the degree of airway obstruction and the number of exacerbations during the previous year. COPD patients categorized as frequent exacerbators were enriched with the bacterial genera Pseudomonas which, in turn, was positively associated with the severity of airflow limitation and the prior year's exacerbation history. The associative relationships of the sputum microbiome with the severity of the disease emphasize the relevance of the interaction between the respiratory microbiota and systemic inflammation. [ABSTRACT FROM AUTHOR]

Background: Asthma is a chronic inflammatory condition characterized by episodes of acute asthma exacerbations (AAEs), in addition to chronic airway inflammation, which has a huge impact on both the affected patients and their parents. The main objective of this study was to explore the utility of available white-blood-cell-derived inflammatory markers in diagnosing AAEs and identifying children at risk for severe exacerbations requiring admission to the pediatric intensive care unit (PICU). Methods: This study was a retrospective cohort study. The medical records of 128 children diagnosed with asthma exacerbation and 131 children with stable asthma between the ages of 2 and 12 years were reviewed. Results: A total of 259 participants were enrolled. Children with AAE demonstrated significantly higher white blood cell counts (WBC: 10.0 ± 4.2 × 103/μL vs. 7.1 ± 2.2 × 103/μL, p < 0.001), absolute neutrophil counts (ANC: 7398.5 ± 4600 cells/μL vs. 2634.8 ± 1448 cells/μL, p < 0.001), and neutrophil-to-lymphocyte ratios (NLR: 7.0 ± 6.8 vs. 0.9 ± 0.7, p < 0.001) but significantly lower absolute lymphocyte counts (ALC: 1794.1 ± 1536 × 103/μL vs. 3552.9 ± 1509 × 103/μL, p < 0.001). Interestingly, blood eosinophil count displayed an opposite trend: children with stable asthma had significantly more eosinophils compared to those experiencing an exacerbation (370.1 ± 342.7 cells/mm3 vs. 0.9 ± 1.9 cells/mm3, p < 0.001). Two criteria that are indicative of AAE were identified: NLR values greater than 1.2, with good discriminative ability (area under the curve [AUC] 0.90; 95% confidence interval [CI] 0.85–0.94; sensitivity 82.5%; specificity 79.5%), and ANC values exceeding 3866, with moderate discriminative ability (AUC 0.86; 95% CI 0.81–0.91; sensitivity 75.0%; specificity 82.3%). Moreover, a comparative analysis of these markers (NLR, ANC, PLR, WBC, AEC, and ALC) in patients with AAE did not demonstrate significant differences between those requiring PICU admission and those who did not require it. Conclusions: This study contributes two major findings. The first is that NLR, ANC, WBC, and PLR are significantly higher in AAE patients compared to those with stable asthma. The second is that children with stable asthma have higher AEC and ALC levels compared to those with AAE. Furthermore, this study has revealed that the studied markers (NLR, ANC, PLR, WBC, AEC, and ALC) did not differentiate between AAE patients requiring PICU admission and those managed in the general ward, suggesting a need for alternative predictive factors. [ABSTRACT FROM AUTHOR]

(1) Shigella spp. (Shigella) is known for causing dysentery with blood in stool, but most children infected with Shigella have non-dysentery Shigella-associated diarrhea (NDSD). The World Health Organization recommends the use of antibiotics when diarrhea is bloody, leaving most NDSD cases untreated. The absence of dysentery may not indicate a low risk of death and severe morbidity. Rapid diagnosis and treatment of shigellosis in vulnerable, young children may be lifesaving. INSIGHT aims to determine the potential benefit of identifying NDSD cases (n = 296) and their outcomes compared to cases of Shigella dysentery [DS (n = 148)] and non-Shigella watery diarrhea [WD (n = 148)]. (2) Children seeking care at hospitals in Bangladesh will be enrolled and followed for 1 year (NDSD and DS) or 90 days (WD). We will determine the impact of NDSD on morbidity, mortality, gut health, nutritional status, and cognitive development compared to DS and WD in children and whether the simple "Rapid LAMP-based Diagnostic Test (RLDT)" can accelerate the detection and treatment of shigellosis in the clinical settings of rural Bangladesh. (3) INSIGHT will determine the impact of NDSD in children and determine if the treatment guidelines of shigellosis need to be revisited to improve clinical outcomes and the development of these children. [ABSTRACT FROM AUTHOR]

To test the hypothesis that they serve as systemic biomarkers of chronic obstructive pulmonary disease (COPD), we profiled the mRNA expression of enzymes connected to systemic inflammation and GSH metabolism in peripheral blood mononuclear cells (PBMCs). These were taken from patients displaying acute exacerbation of COPD (AE-COPD) and stable COPD, and also from non-obstructive smokers and non-smokers. The expression of poly(ADP-ribose) polymerase-1 was increased, but that of histone deacetylase 2 was decreased in association with AE-COPD. The expression of modulatory subunit of glutamyl–cysteine ligase was higher and that of its catalytic subunit, together with the expression of dipeptidyl peptidase 4, was lower in COPD patients compared with non-obstructive smokers and non-smokers. Leukotriene A4 hydrolase saw increased expression in patients with COPD according to disease severity compared to non-obstructive individuals, whereas the expression of GSH peroxidase increased in non-obstructive smokers and COPD patients with the growing number of pack-years smoked. The results corroborate COPD and its acute exacerbation as a complex systemic disorder demonstrating distinct associations with the expression of enzymes linked to inflammation and the regulation of GSH metabolism. [ABSTRACT FROM AUTHOR]

Yijia Guo,1– 3,&ast; Ruyun Zhang,4,&ast; Xinling Gan,5 Erli Wang,6 Shuihua Lu,7 Hui Jiang,3 Hongfei Duan,8 Zhengzhou Yuan,9 Weimin Li,2,3,10 Yong Liu1 1Department of Neurology, Chengdu Medical College, The First Affiliated Hospital, Chengdu, People’s Republic of China; 2Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Emergency, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Department of Radiology, The First People’s Hospital of Longquanyi District, Chengdu, People’s Republic of China; 7National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 8Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 9Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 10National Tuberculosis Clinical Laboratory of China, Beijing Key Laboratory in Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this work as first authorsCorrespondence: Yong Liu, Chengdu Medical College, The First Affiliated Hospital, No. 278, Middle Section, Baoguang Avenue, Xindu District, Chengdu, 610500, People’s Republic of China, Email 410578100@qq.comBackground: The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment.Methods: Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels.Results: A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14– 1.33; P< 0.001), and poor outcome (OR=1.34; 95% CI, 1.26– 1.45; P< 0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42– 1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49– 2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification.Conclusion: Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies.Keywords: tuberculous meningitis, systemic inflammation, neurological outcome

Abstract Background Uric acid (UA), the terminal breakdown product of purine metabolism, possesses contradictory roles, functioning both as an inflammatory mediator and as an antioxidant. Its clinical relevance, particularly in geriatric populations, remains a topic of ongoing debate. Aiming to elucidate whether circulating UA is detrimental or beneficial to human health, we investigate the association between serum UA concentrations and the frailty index—a comprehensive measure of biological aging in a nationally representative cohort of community‐dwelling older adults. Methods We conducted a population‐based, cross‐sectional study utilizing data from the Korea National Health and Nutrition Examination Survey. The sample included 4268 participants aged 65 years and above. A deficit accumulation frailty index (FI) was constructed using 38 items that assess physical, cognitive, psychological, and social domains. Based on the FI, participants were categorized into non‐frail (FI ≤ 0.15), pre‐frail (0.15 0.25). Serum UA levels were quantified through a colorimetric enzymatic assay. Results After controlling for confounders such as age, sex, socioeconomic status (including income and education level), lifestyle factors (smoking status), and medical history (hypertension, diabetes, dyslipidemia, stroke, cardiovascular diseases), and body mass index, serum UA levels were observed to be significantly higher in frail participants compared with their non‐frail counterparts (P

There has been significant increase in mental disorders prevalence in pediatric population around the world. Increasing incidence of autism, intellectual incapacity, hyperkinetic disorders, and schizophrenia gives causes for specific concern. Clarifying mental disorders’ etiology and pathogenesis is the priority of researchers. The role of systemic inflammation in psychiatric disorders development currently remains the least studied. However, it can already be stated that generalized peripheral inflammation is the important factor associated with the development of mental disorders both in adults and children. This review presents latest data, as well as an authors’ assessment of systemic inflammation role in the most common mental disorders development in children. Comparative analysis of acute and chronic systemic inflammation manifestations has been performed. The major pathogenetic mechanisms of “systemic damage” in mental disorders have been identified.

Abstract Background There is no consensus on the cause and effect of systemic chronic inflammation (SCI) regarding chronic obstructive pulmonary disease (COPD). The impact of second-hand smoke (SHS) on COPD has reached inconsistent conclusions. Methods The China Kadoorie Biobank cohort was followed up from the 2004–08 baseline survey to 31 December 2018. Among the selected 445,523 participants in the final analysis, Cox and linear regressions were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of tobacco exposure with COPD risk and baseline levels of log-transformed inflammatory factors [βs (95% CIs)], respectively. Results Participants were followed up for a median of 12.1 years and 11,825 incident COPD events were documented. Ever-smokers were associated with a higher risk of COPD than non-smokers with non-weekly SHS exposure. A younger age to start smoking, a greater amount of daily tobacco consumption, and deeper inhalation were associated with increased risk of COPD and correlated with elevated levels of plasma high-sensitivity C-reactive protein (hs-CRP, all P trend

Background. Currently, the pathophysiological mechanisms of acute damage to organs and systems caused by coronavirus infection have been studied quite fully, but the mechanisms underlying the clinical manifestations of long COVID have not yet been accurately described. The mechanisms of persistence of a number of symptoms in patients who have had COVID-19 and the role of systemic inflammation and endotoxemia markers in it remain a understudied aspect and a promising direction for further studying.The aim of the study. To assess the markers of systemic inflammation, endotoxin-releasing systems, intestinal permeability and endothelial dysfunction in patients with long COVID at the stage of health resort treatment.Methods. The study included 32 patients who had recovered from coronavirus infection and were undergoing health resort treatment in the pulmonology department of the I.M. Sechenov Academic Research Institute for Physical Therapy, Medical Climatology and Rehabilitation. We also selected a control group (n = 20). All patients underwent peripheral blood analysis to detect the levels of markers of systemic inflammation, endotoxin-releasing systems, intestinal permeability, endothelial dysfunction and vasoconstrictor agents: C-reactive protein (CRP), lipopolysaccharide-binding protein (LPB), tissue-type plasminogen activator (tPA), zonulin, bactericidal/ permeability-increasing protein (BPI), vasopressors of angiotensin 2 and endothelin (EDN1).Results. Patients who had recovered from coronavirus infection had a statistically significant increase in the levels of CRP (3.4 [2.56; 4.0] mg/l), LBP (18.46 [14.0; 25.5] ng/ml), tPA (0.07 [0.02; 0.32] ng/ml), angiotensin 2 (133.3 [63.0; 503.7] pg/ml) and a decrease in the level of BPI (1576 [276; 3588] pg/ml) (p < 0.05).Conclusion. A statistically significant increase in markers of systemic inflammation, endotoxinemia, and vasoconstrictor agents in patients with long COVID indicates an imbalance in endotoxin-binding and endotoxin-releasing systems in patients who have had coronavirus infection. Further study of the described markers is necessary to improve approaches to long-term personalized therapy for this category of patients.

The review presents contradictory results from numerous clinical and epidemiological studies, giving reason to doubt the indisputability of ideas about the primary role of low-density lipoprotein (LP) cholesterol in atherogenesis and the efficacy of lipid-lowering therapy. The latter clearly demonstrates the absence of the expected clinical effect in reducing cholesterol levels after surgical correction of lipid metabolism (ileal bypass surgery) or a very modest effect when using drugs devoid of pleiotropic properties. This circumstance finds an explanation in the fact that, according to modern concepts, only modified LP are the molecular substrate of the pathophysiological process at all stages of atherosclerosis development. Native (intact) LP, the concentration of which in the blood does not correlate with the level of modified forms, are not included in the pathogenesis of atherosclerosis. Consequently, the presence of native LP in the blood does not give a true picture of the activity of the atherosclerotic process. Based on the above, in the treatment of atherosclerosis, it should be considered justified not so much to further improve methods of lipid-lowering effects on the body, which do not have a sufficiently reliable evidence base of clinical effect, but to search for means that prevent the generation of atherogenic, modified LP. In this regard, taking into account the important role of systemic inflammation in the pathogenesis of atherosclerosis, the synthesis and clinical use of safe anti-inflammatory drugs, as well as the development and implementation of methods aimed at eliminating the causes of systemic inflammation, should be considered promising.

Background: Intestinal barrier dysfunction and systemic inflammation are common in obstructive sleep apnoea (OSA). We aimed to investigate the role of melatonin, an anti-inflammatory mediator, in mediating the relationships between OSA, intestinal barrier dysfunction and systemic inflammation. Methods: Two hundred and thirty-five male participants who complained with sleep problems and underwent whole night polysomnography at our sleep centre between 2017 and 2018 were enrolled. Polysomnographic data, anthropometric measurements and biochemical indicators were collected. Serum melatonin, intestinal barrier function biomarker zonula occludens-1 (ZO-1) and inflammatory biomarkers C-reactive protein (CRP) with lipopolysaccharide (LPS) were detected. Spearman's correlation analysis assessed the correlations between sleep parameters, melatonin and biomarkers (ZO-1, LPS and CRP). Mediation analysis explored the effect of OSA on intestinal barrier dysfunction and systemic inflammation in moderate-severe OSA patients. Results: As OSA severity increased, serum melatonin decreased, whereas ZO-1, LPS and CRP increased. Spearman's correlation analysis showed that serum melatonin was significantly negatively correlated with ZO-1 (r = -0.19, p < .05) and LPS (r = -0.20, p < .05) in the moderate-OSA group; serum melatonin was significantly negatively correlated with ZO-1 (r = -0.46, p < .01), LPS (r = -0.35, p < .01) and CPR (r = -0.30, p < .05) in the severe-OSA group. Mediation analyses showed melatonin explain 36.12% and 35.38% of the effect of apnoea-hypopnea index (AHI) on ZO-1 and LPS in moderate to severe OSA patients. Conclusions: Our study revealed that melatonin may be involved in mediating intestinal barrier dysfunction and systemic inflammation in moderate-to-severe OSA patients. [ABSTRACT FROM AUTHOR]

Background. It is known that COVID-19 can be followed by a shift in the hemostatic system towards hypercoagulation, which is more pronounced in the presence of diabetes mellitus (DM). Tuberculosis process is often accompanied with hypercoagulation syndrome. Of great interest is the study of the state of hemostatic systems in patients with pulmonary tuberculosis (TB) with concomitant DM who have had COVID-19.The aim. To study the relationship between the state of the hemostatic and fibrinolysis systems and moderate and severe COVID-19 in patients with pulmonary tuberculosis and diabetes mellitus.Methods. 32 patients with TB and DM were divided into two groups. Group 1 included 16 patients with TB and DM who have previously had COVID-19 (TB-DM-COVID). Group 2 included 16 patients with TB and DM who did not have COVID-19 (TB-DM).Results. It was found that TB-DM-COVID patients were more likely to develop a hypercoagulable shift compared to TB-DM patients. This was evidenced by a more frequent shortening of such indicator as activated partial thromboplastin time (43.7 % and 25.0 % of cases, respectively; χ2 = 7.22; p = 0.01), an increase in fibrinogen levels (43.7 % and 25.0%, respectively; χ2 = 7.22; p = 0.01) and D-dimer (43.7 % and 18.7 %, respectively; χ2 = 14.74; p = 0.0001). These changes were closely associated with the systemic inflammatory response, as strong and positive correlations were found between fibrinogen and C-reactive protein levels (r = 0.420; p = 0.01), and erythrocyte sedimentation rate (r = 0.433; p = 0.01) in TB-DM-COVID patients.Conclusion. In patients with pulmonary tuberculosis and diabetes mellitus after moderate and severe COVID-19, compared to patients who have not had COV ID-19, a hypercoagulable shift associated with the development of more pronounced systemic inflammation develops more often.

BACKGOUND: Inflammatory hematological ratios (IHRs), such as neutrophil to lymphocyte, monocyte to lymphocyte, and platelet to lymphocyte ratios, are associated with mental disorders, symptoms severity, and the disease phase. Evidence from the studies in adult patients has been summarized in systematic reviews and meta-analyses. The results of the studies in adolescents remain poorly systematized. AIM: To summarize the findings from the studies that investigated the relationship of IHRs with mental disorders in adolescent patients. METHODS: This scoping review included studies of IHRs in patients aged 10–19 years with mental disorders (other than anorexia nervosa), published in English by December 31, 2023. The search for relevant papers was performed in MEDLINE. The studies were categorized into two groups: studies with external controls (healthy adolescents) and studies with internal controls (patients in different phases of mental disorder, with or without self-harm/suicidal behaviors). RESULTS: A total of 11 studies were included in the review (all cross-sectional ones). The results of these studies demonstrate that 1) adolescents with mental disorders (major depressive disorder, psychotic disorders, obsessive-compulsive disorder, attention deficit hyperactivity disorder, substance use disorders) have higher IHR values than individuals of the same age without corresponding disorders (5 studies); 2) IHR values are positively correlated with the severity of psychopathological symptoms (1 study); 3) higher IHR values are associated with the phase of the mental disorder — manic episode in bipolar disorder (1 study) and exacerbation of psychosis in psychotic disorders (1 study); and 4) higher IHR values are associated with self-harm/suicidal behaviors — suicide attempts (1 study) and non-suicidal self-injury (1 study). CONCLUSION: IHRs are associated with mental disorders in adolescents, and higher IHR values are associated with a more severe/acute clinical presentation (severity of symptoms, mania, acute psychosis, self-harm/suicidal behaviors). Further studies of higher methodological quality are needed to evaluate the diagnostic and prognostic value of IHRs as biomarkers of mental disorders in adolescence.

Abstract In this study, we examined how systemic inflammation affects repair of brain injury. To this end, we created a brain-injury model by stereotaxic injection of ATP, a damage-associated molecular pattern component, into the striatum of mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS-ip). An analysis of magnetic resonance images showed that LPS-ip reduced the initial brain injury but slowed injury repair. An immunostaining analysis using the neuronal marker, NeuN, showed that LPS-ip delayed removal of dead/dying neurons, despite the fact that LPS-ip enhanced infiltration of monocytes, which serve to phagocytize dead cells/debris. Notably, infiltrating monocytes showed a widely scattered distribution. Bulk RNAseq analyses showed that LPS-ip decreased expression of genes associated with phagocytosis, with PCR and immunostaining of injured brains confirming reduced levels of Cd68 and Clec7a, markers of phagocytic activity, in monocytes. Collectively, these results suggest that systemic inflammation affects properties of blood monocytes as well as brain cells, resulting in delay in clearing damaged cells and activating repair processes.

Abstract Systemic inflammation generally coexists with functional limitations that seriously affect quality of life. This study aimed to investigate the association between systemic inflammation in midlife and the risk of functional limitations in late-life. A total of 10,044 participants with an average age of 53.9 ± 5.7 years at baseline were included in a cohort study. At the last follow-up, the prevalence of impaired activities of daily living (ADLs), instrumental activities of daily living (IADLs), and lower extremity function (LEF) was 14.7%, 21.6%, and 50.3%, respectively. The values of four inflammatory biomarkers were used to calculate the inflammation composite score. Compared with the participants in the lowest quartile of the inflammation composite score (Q1), those in the highest quartile (Q4) exhibited an odds ratio (OR) of 1.589 and a 95% confidence interval (CI) of 1.335–1.892 for impaired ADLs, an OR of 1.426 and a 95% CI of 1.228–1.657 for impaired IADLs, and an OR of 1.728 and a 95% CI of 1.526–1.957 for impaired LEF. The association between systemic inflammation and functional limitations was partly mediated by cardiac and brain function. The present study provides evidence that systemic inflammation in midlife is associated with a higher risk of late-life functional limitations. Protecting vital organ functions in midlife may have a positive impact on reducing the risk of future functional limitations. Trial registration: www.clinicaltrials.gov ; Unique identifier: NCT00005131.

Numerous biomarkers that reflect host status have been identified for patients with metastatic colorectal cancer (mCRC). However, there has been a paucity of biomarker studies that comprehensively indicate body composition, nutritional assessment, and systemic inflammation status. The advanced lung cancer inflammation index (ALI), initially introduced as a screening tool for patients with non-small-cell lung cancer in 2013, emerges as a holistic marker encompassing all body composition, nutritional status, and systemic inflammation status. The index is calculated by the simple formula: body mass index × albumin value / neutrophil-to-lymphocyte ratio. Given its accessibility in routine clinical practice, the ALI has exhibited promising clinical utility in prognosticating outcomes for patients with multiple types of cancer. In this review, we focus on the significance of host status and the clinical applicability of the ALI in the treatment and management of patients with malignancies, including mCRC. We also suggest its potential in guiding the formulation of treatment strategies against mCRC and outline future perspectives.

Introduction. Chemotherapy in combination with targeted therapy (CT + TT) using a monoclonal antibody against epidermal growth factor receptor (EGFR) cetuximab and subsequent maintenance targeted therapy (CT + TT/TT) is the leading 1st line therapy of recurrent/metastatic head and neck squamous cell carcinoma to achieve objective response irrespective of programmed cell death-ligand 1 (pD-L1) expression level. However, often in clinical practice patient profile does not match characteristics of patients included in registration studies. Therapy selection is based on massive advancement of the tumor, low performance status of the patient, use of various chemotherapy regimes which often decreases therapy effectiveness. This creates a necessity of identification of clinical markers of effectiveness based on the drug's pharmacodynamics and mechanism of action.Aim. To analyze the effect of clinical characteristics, peripheral blood markers, and systemic inflammation on long-term results of CT + TT/TT with cetuximab in cancer of the mucosa of the head and neck.Materials and methods. The prospective observational study performed at the Oncology Department with a course on thoracic surgery of the Kuban State Medical University, included 52 patients with head and neck squamous cell carcinoma receiving CT + TT/TT between 2020 and 2023. Clinical characteristics and results of peripheral blood tests were retrospectively analyzed, indices of inflammatory reaction prior to treatment and 12-16 weeks after CT + TT/TT with cetuximab were calculated. Statistical analysis was performed using the med Calc ver. 20.218 and IBM SPSS Statistics 22 software.Results. CT + TT/TT with cetuximab significantly increased red blood cell count (RBC), lymphocyte-monocyte ratio (LMR), and decreased systemic inflammatory markers (SIM) (p 3.27 after 12-16 weeks of therapy (AUC = 0.685; 95 % CI 0.486-0.885; p = 0.0691). median survival of patients after the start of CT + TT/TT with cetuximab was 28 months (95 % CI 17-48), progression-free survival was 8 months (95 % CI 5-36). For RBC count >3.8 x 1012/L 12-16 weeks after the start of therapy, risk of progression decreased by 79 % (hazard ratio 0.21; 95 % CI 0.07-0.62; p = 0.0047). Partial response after 12-16 weeks of CT + TT/TT decreased progression risk more than 4-fold (p

Abstract Background Chronic inflammation may contribute to increased mortality risk in individuals with osteoarthritis (OA), but research on the prognostic value of inflammatory biomarkers is limited. We aimed to evaluate the associations of the systemic immune–inflammation index (SII) and systemic inflammation response index (SIRI) with all-cause and cardiovascular mortality among US adults with OA. Methods This cohort study included 3545 adults with OA aged ≥ 20 years from the National Health and Nutrition Examination Survey 1999–2020. The SII and SIRI were calculated using complete blood cell count data. Participants were categorized as having a higher or lower SII and SIRI using cutoff points derived by the maximally selected rank statistics method. Cox proportional hazards models, Fine–Gray competing risk regression models and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the associations between the SII/SIRI and mortality in OA patients. Results Over a median follow-up of 5.08 (3.42–9.92) years, 636 (17.94%) deaths occurred, including 149 (4.20%) cardiovascular deaths. According to multivariable-adjusted models involving demographic, socioeconomic, and health factors, OA patients with a higher SII had a twofold greater risk of all-cause mortality than patients with a lower SII (HR 2.01; 95% CI: 1.50–2.68). Similarly, a higher SIRI was associated with an 86% increased risk of all-cause mortality relative to a lower SIRI (HR 1.86; 95% CI: 1.46–2.38). Similar to the trend found with all-cause mortality, patients with an elevated SII and SIRI had a 88% and 67% increased risk of cardiovascular mortality, respectively, compared to patients with a lower SII (HR 1.88; 95% CI: 1.16–3.03) and SIRI (HR 1.67; 95% CI: 1.14–2.44). Time-dependent ROC curves showed that both the SII and SIRI have moderate and valid performance in predicting short- and long-term mortality in patients with OA. Conclusions Higher SII and SIRI values were associated with greater all-cause and cardiovascular mortality among US adults with OA.

Abstract Background Systemic inflammation and frailty have been implicated in osteoporosis (OP) and fracture risks; however, existing evidence remains limited and inconclusive. This study aimed to assess the associations of systemic inflammation and frailty phenotype with incident OP and fracture and to evaluate the mediating role of frailty phenotype. Methods The present study analysed data from the UK Biobank, a comprehensive and representative dataset encompassing over 500 000 individuals from the general population. Baseline peripheral blood cell counts were employed to calculate the systemic inflammation markers, including neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR) and systemic immune‐inflammation index (SII). Frailty phenotype was assessed using five criteria, defined as frail (≥3 items met), pre‐frail (1–2 items met) and non‐frail (0 items met). OP and fracture events were confirmed through participants' health‐related records. Multivariable linear and Cox regression models were utilized, along with mediation analysis. Results Increased systemic inflammation was associated with increased risks of OP and fracture. The corresponding hazard ratios and 95% confidence intervals (CIs) for OP risk per standard deviation increase in the log‐transformed NLR, PLR and SII were 1.113 (1.093–1.132), 1.098 (1.079–1.118) and 1.092 (1.073–1.111), and for fracture risk, they were 1.066 (1.051–1.082), 1.059 (1.044–1.075) and 1.073 (1.058–1.089), respectively. Compared with the non‐frail individuals, the pre‐frail and frail ones showed an elevated OP risk by 21.2% (95% CI: 16.5–26.2%) and 111.0% (95% CI: 98.1–124.8%), respectively, and an elevated fracture risk by 6.1% (95% CI: 2.8–9.5%) and 38.2% (95% CI: 30.7–46.2%), respectively. The systemic inflammation level demonstrated a positive association with frailty, with β (95% CI) of 0.034 (0.031–0.037), 0.026 (0.023–0.029) and 0.008 (0.005–0.011) in response to per standard deviation increment in log‐transformed SII, NLR and PLR, respectively. The frailty phenotype mediated the association between systemic inflammation and OP/fracture risk. Subgroup and sensitivity analyses confirmed the robustness of these findings. Conclusions Systemic inflammation and frailty phenotype are independently linked to increased risks of OP and fracture. The frailty phenotype partially mediates the association between systemic inflammation and osteoporotic traits. These results highlight the significance of interventions targeting systemic inflammation and frailty in OP and fracture prevention and management.

Jing-Feng Zou,&ast; Shao-Tian Li,&ast; Li-Ping Wang,&ast; Nian-Li Zhou, Jia-Jia Ran, Xin Yang, Chun-Hui Tian, Yi-Ting Liu, Yun Liu, Wen Peng Department of General Practice, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, WuHan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Liu; Wen Peng, Department of General Practice, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jie Fang Avenue, WuHan, Hubei, 1227, People’s Republic of China, Email 8735225@qq.com; pengwen666@sina.comBackground: Emerging evidence suggests that systemic inflammatory and nutritional biomarkers, along with derived indices, could serve as predictors for sarcopenia in cancer population. This study aimed to compare these predictors, focusing on the nutritional risk index (NRI) and evaluate its diagnostic value, for sarcopenic patients without cancer.Methods: This cross-sectional retrospective study included 1674 participants. Sarcopenia is defined by skeletal muscle mass index (SMI). Laboratory data reflected the values of systemic inflammatory and nutritional biomarkers, from which the derived indices were calculated. Multiple logistic regression analysis, ROC curve analysis, and the Youden index were utilized to assess the association between these markers and sarcopenia and determine the cutoff value for predicting sarcopenia.Results: Among all participants (1110 men and 564 women, mean age 61.97 ± 9.83 years), 398 individuals were diagnosed with sarcopenia, indicating a prevalence of 23.78% in China’s middle-aged and elderly population without cancer. Logistic regression analysis revealed significant associations between all biomarkers and derived indices with sarcopenia. Following adjustment for potential confounders, lower NRI values were significantly associated with a higher incidence of sarcopenia. For sarcopenia diagnosis, the area under the curve (AUC) for NRI was 0.769 ([95% CI, 0.742, 0.796], P < 0.001), with a cutoff value of 106.016, sensitivity of 75.6% and specificity of 66.1%. NRI demonstrated greater predictive advantage for sarcopenia incidence in men compared to women.Conclusion: A lower NRI value was associated with a higher prevalence of sarcopenia. NRI shows promise for early, rapid, and effective sarcopenia screening, particularly in China’s middle-aged and elderly male population without cancer.Keywords: sarcopenia, systemic inflammation, nutritional risk index, NRI

Background: Biomarkers associated with disease severity and comorbid metabolic syndrome (MetS) in patients with hidradenitis suppurativa (HS) are lacking. Objective: To identify biomarkers associated with disease severity and comorbid MetS in patients with HS. Methods: Data on hospital outpatients with HS were obtained through clinical examination and interviews. Indicators of systemic inflammation; C-reactive protein (CRP), erythrocyte sedimentation-rate (ESR), neutrophil/lymphocyte-ratio (NLR), platelet/lymphocyte-ratio (PLR), monocyte/lymphocyte-ratio (MLR), platelet/neutrophil-ratio (PNR), pan-immune-inflammation-value (PIV), and systemic-immune-inflammatory-index (SII), were calculated from blood samples. Results: Seven hundred patients were included; of those 444 (63.4%) and 256 (36.6%) were female and male, respectively, with a median age of 38.3 years (IQR = 27.9-51.0). Increasing CRP, ESR, NLR, PIV, and SII (P

Abstract Cancer cachexia (CC) is a debilitating syndrome that affects 50–80% of cancer patients, varying in incidence by cancer type and significantly diminishing their quality of life. This multifactorial syndrome is characterized by muscle and fat loss, systemic inflammation, and metabolic imbalance. Extracellular vesicles (EVs), including exosomes and microvesicles, play a crucial role in the progression of CC. These vesicles, produced by cancer cells and others within the tumor environment, facilitate intercellular communication by transferring proteins, lipids, and nucleic acids. A comprehensive review of the literature from databases such as PubMed, Scopus, and Web of Science reveals insights into the formation, release, and uptake of EVs in CC, underscoring their potential as diagnostic and prognostic biomarkers. The review also explores therapeutic strategies targeting EVs, which include modifying their release and content, utilizing them for drug delivery, genetically altering their contents, and inhibiting key cachexia pathways. Understanding the role of EVs in CC opens new avenues for diagnostic and therapeutic approaches, potentially mitigating the syndrome’s impact on patient survival and quality of life.

Abstract Systemic inflammation and neuroinflammation affect the natural course of the sporadic form of Alzheimer’s disease (AD), as supported by epidemiological and preclinical data, and several epidemiological studies indicate a higher prevalence of AD in patients with inflammatory bowel disease. In this study, we explored whether colitis induced by dextran sulfate sodium (DSS) in young, presymptomatic/preplaque mice worsens and/or anticipates age-dependent cognitive impairment in Tg2576, a widely used mouse model of AD. We demonstrated that DSS colitis induced in young Tg2576 mice anticipates the onset age of learning and memory deficit in the Morris water maze test. To explore potential mechanisms behind the acceleration of cognitive decline in Tg2576 mice by DSS colitis, we focused on gut microbiota, systemic inflammation and neuroinflammation markers. We observed a Firmicutes/Bacteroidetes ratio change in Tg2576 DSS animals comparable to that of elderly Tg2576 mice, suggesting accelerated microbiota aging in Tg2576 DSS mice, a change not observed in C57BL6 DSS mice. We also observed substantial differences between Tg2576 and WT mice in several inflammation and neuroinflammation-related parameters as early as 3 months of age, well before plaque deposition, a picture which evolved rapidly (between 3 and 5.5 months of age) in contrast to Tg2576 and WT littermates not treated with DSS. In detail, following induction of DSS colitis, WT and Tg2576 mice exhibited contrasting features in the expression level of inflammation-evoked astrocyte-associated genes in the hippocampus. No changes in microglial features occurred in the hippocampus between the experimental groups, whereas a reduced glial fibrillary acidic protein immunoreactivity was observed in Tg2576 vs. WT mice. This finding may reflect an atrophic, “loss-of-function” profile, further exacerbated by DSS where a decreased of GFAP mRNA expression level was detected. In conclusion, we suggest that as-yet unidentified peripheral mediators evoked by DSS colitis and involving the gut-brain axis emphasize an astrocyte “loss-of-function” profile present in young Tg2576 mice, leading to impaired synaptic morphological and functional integrity as a very early sign of AD.

Systemic inflammation generally coexists with functional limitations that seriously affect quality of life. This study aimed to investigate the association between systemic inflammation in midlife and the risk of functional limitations in late-life. A total of 10,044 participants with an average age of 53.9 ± 5.7 years at baseline were included in a cohort study. At the last follow-up, the prevalence of impaired activities of daily living (ADLs), instrumental activities of daily living (IADLs), and lower extremity function (LEF) was 14.7%, 21.6%, and 50.3%, respectively. The values of four inflammatory biomarkers were used to calculate the inflammation composite score. Compared with the participants in the lowest quartile of the inflammation composite score (Q1), those in the highest quartile (Q4) exhibited an odds ratio (OR) of 1.589 and a 95% confidence interval (CI) of 1.335–1.892 for impaired ADLs, an OR of 1.426 and a 95% CI of 1.228–1.657 for impaired IADLs, and an OR of 1.728 and a 95% CI of 1.526–1.957 for impaired LEF. The association between systemic inflammation and functional limitations was partly mediated by cardiac and brain function. The present study provides evidence that systemic inflammation in midlife is associated with a higher risk of late-life functional limitations. Protecting vital organ functions in midlife may have a positive impact on reducing the risk of future functional limitations. Trial registration: www.clinicaltrials.gov; Unique identifier: NCT00005131. [ABSTRACT FROM AUTHOR]

In this study, we examined how systemic inflammation affects repair of brain injury. To this end, we created a brain-injury model by stereotaxic injection of ATP, a damage-associated molecular pattern component, into the striatum of mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS-ip). An analysis of magnetic resonance images showed that LPS-ip reduced the initial brain injury but slowed injury repair. An immunostaining analysis using the neuronal marker, NeuN, showed that LPS-ip delayed removal of dead/dying neurons, despite the fact that LPS-ip enhanced infiltration of monocytes, which serve to phagocytize dead cells/debris. Notably, infiltrating monocytes showed a widely scattered distribution. Bulk RNAseq analyses showed that LPS-ip decreased expression of genes associated with phagocytosis, with PCR and immunostaining of injured brains confirming reduced levels of Cd68 and Clec7a, markers of phagocytic activity, in monocytes. Collectively, these results suggest that systemic inflammation affects properties of blood monocytes as well as brain cells, resulting in delay in clearing damaged cells and activating repair processes. [ABSTRACT FROM AUTHOR]

The association of Healthy Eating Index 2020 (HEI‐2020), especially its components with systemic inflammatory biomarkers, has not been examined. The aim of this study was to investigate the relationship between HEI‐2020 and its components with systemic inflammatory biomarkers, and to provide a dietary pattern suggestion to combat systemic inflammation. Participants aged 20 years and older with complete information on two reliable dietary recalls, blood cell counts and demographic characteristics, were recruited from six NHANES cycles from 2007 to 2018. Weighted general linear methods showed that HEI‐2020 was negatively associated with systemic immune‐inflammation index (SII) and systemic inflammation response index (SIRI). Weighted quantile regression (WQS) models and quantile g‐computation (QGC) models supported the negative association between the mixed components and systemic inflammation. High intakes of whole fruits, whole grains, greens and beans, and seafood and plant proteins, along with a low intake of added sugars, were associated with reduced systemic inflammation. In contrast, the scores of sodium, dairy, total protein, and refined grains showed no significant effect. Briefly, our study provides an anti‐inflammatory dietary pattern suggestion based on the 13 components of HEI‐2020 and Dietary Guidelines for Americans. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a severe medical condition resulting in substantial physiological and functional consequences for the individual. People with SCI are characterised by a chronic, low-grade systemic inflammatory state, which contributes to further undesirable secondary injuries. This study aimed to evaluate the effect of adding aquatic therapy to the standard physiotherapy treatment, implemented in two different schedules, on systemic inflammation in SCI patients. Additionally, the relationship between cytokine blood levels and changes in functionality (measured with the 6MWT, 10MWT, WISCI, BBS, and TUG tests) throughout the study was assessed. A quantitative multiplexed antibody assay was performed to measure the expression level of 20 pro- and anti-inflammatory cytokines in blood samples from SCI patients at three time points: baseline, week 6, and immediately post-intervention (week 12). This study identified a complex signature of five cytokines (IL-12p70, IL-8, MCP-1, IL-1α, and IP10) associated with the time course of the two physiotherapy programs. Two other cytokines (IL-4 and TNF-α) were also associated with the functional recovery of patients. These could be important indicators for SCI prognosis and provide a basis for developing novel targeted therapies. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a multifactorial pregnancy disorder characterized by hypertension and proteinuria, posing significant risks to both maternal and fetal health. Despite extensive research, its complex pathophysiology remains incompletely understood. This narrative review aims to elucidate the intricate mechanisms contributing to PE, focusing on abnormal placentation, maternal systemic response, oxidative stress, inflammation, and genetic and epigenetic factors. This review synthesizes findings from recent studies, clinical trials, and meta-analyses, highlighting key molecular and cellular pathways involved in PE. The review integrates data on oxidative stress biomarkers, angiogenic factors, immune interactions, and mitochondrial dysfunction. PE is initiated by poor placentation due to inadequate trophoblast invasion and improper spiral artery remodeling, leading to placental hypoxia. This triggers the release of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), causing widespread endothelial dysfunction and systemic inflammation. Oxidative stress, mitochondrial abnormalities, and immune dysregulation further exacerbate the condition. Genetic and epigenetic modifications, including polymorphisms in the Fms-like tyrosine kinase 1 (FLT1) gene and altered microRNA (miRNA) expression, play critical roles. Emerging therapeutic strategies targeting oxidative stress, inflammation, angiogenesis, and specific molecular pathways like the heme oxygenase-1/carbon monoxide (HO-1/CO) and cystathionine gamma-lyase/hydrogen sulfide (CSE/H2S) pathways show promise in mitigating preeclampsia's effects. PE is a complex disorder with multifactorial origins involving abnormal placentation, endothelial dysfunction, systemic inflammation, and oxidative stress. Despite advances in understanding its pathophysiology, effective prevention and treatment strategies remain limited. Continued research is essential to develop targeted therapies that can improve outcomes for both mothers and their babies. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate a nomogram for predicting the overall survival of patients with metastatic pancreatic cancer. Methods: This retrospective study included 236 patients with metastatic pancreatic cancer treated at Guangxi Medical University Cancer Hospital between October 2013 and October 2022. Patients were grouped according to hepatitis B virus (HBV) infection status. Cox proportional hazard regression was used to identify the prognostic factors independently associated with overall survival. Results were used to build a nomogram, which was assessed through internal validation using bootstrap resampling. Results: Patients in the HBV-positive group (N = 37) showed significantly better overall survival than those in the HBV-negative group (N=199; P = 0.014). Overall survival was independently associated with the following factors: HBV infection status, sex, chemotherapy, metastatic sites, a combined index of hemoglobin, albumin, lymphocytes, and platelets, neutrophil-albumin ratio, as well as levels of CA125. The nomogram showed good predictive power, with an area under the curve of 0.808 for the time-dependent receiver operating characteristic. Calibration and decision curve analyses indicated good calibration and clinical usefulness of the nomogram for predicting the overall survival of patients with metastatic pancreatic cancer. Conclusion: A nomogram based on the HBV infection status and inflammatory nutritional markers may help predict the overall survival of patients with metastatic pancreatic cancer and guide personalized clinical treatment. [ABSTRACT FROM AUTHOR]

Background: Chronic Kidney Disease (CKD) is linked to systemic inflammation, which may be influenced by the oral microbiome. This study aimed to compare the oral microbiome of CKD patients with that of healthy individuals and examine its impact on systemic inflammation. Materials and Methods: The study included 100 participants: 50 CKD patients and 50 healthy controls. Microbial diversity indices, dominant phyla distribution, and key genera abundances were assessed using high-throughput sequencing. Systemic inflammation markers, such as C-Reactive Protein (CRP), Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α), were measured. Correlation analyses were performed to explore the relationships between microbial abundances and inflammation markers. Results: CKD patients showed significantly lower microbial diversity compared to healthy controls (Shannon Index: 3.2 ± 0.5 vs. 4.1 ± 0.6; Simpson Index: 0.76 ± 0.1 vs. 0.84 ± 0.1). Dominant phyla in CKD patients included Firmicutes (45%), Proteobacteria (30%), Bacteroidetes (15%), and Actinobacteria (10%), while healthy controls had Firmicutes (50%), Bacteroidetes (25%), Actinobacteria (15%), and Proteobacteria (10%). Notable genera differences included higher abundances of Streptococcus and Neisseria in CKD patients and higher abundances of Lactobacillus and Prevotella in healthy controls. Systemic inflammation markers were elevated in CKD patients (CRP: 6.2 mg/L ± 1.2 vs. 2.1 mg/L ± 0.8; IL-6: 8.5 pg/mL ± 1.5 vs. 3.2 pg/mL ± 0.9; TNF-α: 12.4 pg/mL ± 2.1 vs. 5.3 pg/mL ± 1.4). Positive correlation was found between Streptococcus abundance and CRP levels (r = 0.72, p < 0.001), and a negative correlation between Lactobacillus abundance and IL-6 levels (r = -0.65, p < 0.01). Conclusion: CKD patients exhibit altered oral microbiome profiles and increased systemic inflammation. These findings suggest a connection between oral microbiome imbalance and systemic inflammation in CKD, highlighting the importance of further research on potential therapeutic approaches. [ABSTRACT FROM AUTHOR]

Smoke derived from combustible cigarettes (CCs) contains numerous harmful chemicals that can impair the viability, proliferation, and activation of immune cells, affecting the progression of chronic inflammatory diseases. In order to avoid the detrimental effects of cigarette smoking, many CC users have replaced CCs with heated tobacco products (HTPs). Due to different methods of tobacco processing, CC-sourced smoke and HTP-derived aerosols contain different chemical constituents. With the exception of nicotine, HTP-sourced aerosols contain significantly lower amounts of harmful constituents than CC-derived smoke. Since HTP-dependent effects on immune-cell-driven inflammation are still unknown, herein we used flow cytometry analysis, intracellular staining, and an enzyme-linked immunosorbent assay to determine the impact of CCs and HTPs on systemic inflammatory response in patients suffering from ulcerative colitis (UC), diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD). Both CCs and HTPs significantly modulated cytokine production in circulating immune cells, affecting the systemic inflammatory response in COPD, DM, and UC patients. Compared to CCs, HTPs had weaker capacity to induce the synthesis of inflammatory cytokines (IFN-γ, IL-1β, IL-5, IL-6, IL-12, IL-23, IL-17, TNF-α), but more efficiently induced the production of immunosuppressive IL-10 and IL-35. Additionally, HTPs significantly enhanced the synthesis of pro-fibrotic TGF-β. The continuous use of CCs and HTPs aggravated immune-cell-driven systemic inflammation in COPD and DM patients, but not in UC patients, suggesting that the immunomodulatory effects of CC-derived smoke and HTP-sourced aerosols are disease-specific, and need to be determined for specific immune-cell-driven inflammatory diseases. [ABSTRACT FROM AUTHOR]