Identification of State Markers in Anorexia Nervosa: Replication and Extension of Inflammation-Associated Biomarkers Using Multiplex Profiling.

Background: Proteomics offers potential for detecting and monitoring anorexia nervosa (AN) and its variant, atypical AN (atyp-AN). However, research has been limited by small protein panels, a focus on adult AN, and lack of replication. Methods: In this study, we performed Olink multiplex profiling of 92 inflammation-related proteins in females with AN/atyp-AN (n = 64), all of whom were ≤90% of expected body weight, and age-matched healthy control individuals (n = 44). Results: Five proteins differed significantly between the primary AN/atyp-AN group and the healthy control group (lower levels: HGF, IL-18R1, TRANCE; higher levels: CCL23, LIF-R). The expression levels of 3 proteins (lower IL-18R1, TRANCE; higher LIF-R) were uniquely disrupted in participants with AN in our primary model. No unique expression levels emerged for atyp-AN. In the total sample, 12 proteins (ADA, CD5, CD6, CXCL1, FGF-21, HGF, IL-12B, IL18, IL-18R1, SIRT2, TNFSF14, TRANCE) were positively correlated with body mass index and 5 proteins (CCL11, FGF-19, IL8, LIF-R, OPG) were negatively correlated with body mass index in our primary models. Conclusions: Our results replicate the results of a previous study that demonstrated a dysregulated inflammatory status in AN and extend those results to atyp-AN. Of the 17 proteins correlated with body mass index, 11 were replicated from a previous study that used similar methods, highlighting the promise of inflammatory protein expression levels as biomarkers of AN disease monitoring. Our findings underscore the complexity of AN and atyp-AN by highlighting the inability of the identified proteins to differentiate between these 2 subtypes, thereby emphasizing the heterogeneous nature of these disorders.

We examined 73 inflammation proteins in adolescent girls with anorexia nervosa (AN) and atypical AN and compared them with age-matched healthy control girls. Significant differences were found, driven by 5 key proteins (lower: HGF, IL-18R1, TRANCE; higher: CCL23, LIF-R). Three proteins (TRANCE, LIF-R, IL-18R1) uniquely distinguished low-weight participants with AN from control participants. Our study reveals distinct inflammation patterns in AN and atypical AN and sheds light on potential state-specific factors that underlie these disorders.

The association between systemic inflammation markers and paroxysmal atrial fibrillation.

BACKGROUND: Systemic inflammation markers have recently been identified as being associated with cardiac disorders. However, limited research has been conducted to estimate the pre-diagnostic associations between these markers and paroxysmal atrial fibrillation (PAF). Our aim is to identify potential biomarkers for early detection of PAF. METHODS: 91 participants in the PAF group and 97 participants in the non-PAF group were included in this study. We investigated the correlations between three systemic inflammation markers, namely the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), and PAF. RESULTS: The proportion of patients with PAF gradually increased with increasing logSII, logSIRI, and logAISI tertiles. Compared to those in the lowest tertiles, the PAF risks in the highest logSII and logSIRI tertiles were 3.2-fold and 2.9-fold, respectively. Conversely, there was no significant correlation observed between logAISI and PAF risk within the highest tertile of logAISI. The restricted cubic splines (RCS) analysis revealed a non-linear relationship between the elevation of systemic inflammation markers and PAF risk. Specifically, the incidence of PAF is respectively increased by 56%, 95%, and 150% for each standard deviation increase in these variables. The ROC curve analysis of logSII, logSIRI and logAISI showed that they had AUC of 0.6, 0.7 and 0.6, respectively. It also demonstrated favorable sensitivity and specificity of these systemic inflammation markers in detecting the presence of PAF. CONCLUSIONS: In conclusion, our study reveals significant positive correlations between SII, SIRI, and AISI with the incidence of PAF.

Exploring the Impact of Vitamin D Supplementation on Metabolic Syndrome Variables in Postmenopausal Women: A Comprehensive Review.

Metabolic syndrome poses a significant health concern, particularly among postmenopausal women who are vulnerable to its adverse effects. Emerging evidence suggests a potential role of vitamin D in mitigating metabolic syndrome risk factors, prompting interest in its supplementation as a therapeutic intervention. This comprehensive review examines the impact of vitamin D supplementation on metabolic syndrome variables in postmenopausal women. Through a systematic synthesis of existing literature, we assess the evidence supporting the beneficial effects of vitamin D on insulin sensitivity, lipid profiles, and inflammation markers in this population. While findings suggest potential benefits, uncertainties remain regarding optimal dosage and duration of supplementation. Implications for clinical practice underscore the importance of assessing vitamin D status and considering supplementation as part of a comprehensive approach to metabolic health management. Furthermore, public health initiatives promoting adequate vitamin D intake may help mitigate the prevalence of metabolic syndrome and associated complications. However, further research is warranted to elucidate the underlying mechanisms, establish optimal supplementation protocols, and explore potential interactions with other nutrients or medications. Long-term randomized controlled trials are needed to evaluate the sustained effects of vitamin D supplementation on metabolic health outcomes in postmenopausal women.

The Effects of Raspberry Consumption on Glycemic Control and Inflammation Markers in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Despite observing the health benefits of raspberry consumption in some recent studies, there is still no consensus regarding this effectiveness on inflammatory markers and glycemic control. This study aimed to investigate this effectiveness by performing a meta-analysis. The PubMed, Web of Science, and Scopus databases were comprehensively searched until December 2023 to find relevant randomized controlled trials. Eligible studies were screened, and relevant information was extracted. The overall effect size of raspberry consumption on each of the outcomes was estimated by following the random-effects model in the form of a 95% confidence interval (CI) and a weighted mean difference (WMD). Raspberry consumption led to a significant increase in insulin concentrations (WMD: 1.89 µU/mL; 95%CI: 1.45, 2.34; P < 0.001) and a significant decrease in tumor necrosis factor-α (TNF-α) concentrations (WMD: -3.07 pg/mL; 95%CI: -5.17, -0.97; P = 0.004), compared with the control groups. Raspberry consumption did not have a significant effect on fasting blood glucose, insulin, hemoglobin A1C, glucose tolerance tests, homeostatic model assessment for insulin resistance, C-reactive protein, and interleukin-6 concentrations. This review revealed that raspberry consumption led to a significant increase and decrease in insulin and TNF-α concentrations, respectively. However, to draw a more accurate conclusion, it is necessary to conduct studies with a larger sample size in the future. The current study's protocol has been registered in the PROSPERO system as CRD42023477559.

A Mendelian randomization study investigating the causal relationships between inflammation and immunoglobulin A nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is an autoimmune disease characterized by the production of galactose­deficient IgA1 (Gd­IgA1) and the deposition of immune complexes in the kidney. Exploring the landscape of immune dysregulation in IgAN is valuable for pathogenesis and disease treatment. We conducted Mendelian randomization (MR) to assess the causal correlations between inflammation and IgAN. METHODS: Based on available genetic datasets, we investigated potential causal links between inflammation and the risk of IgAN using two-sample MR. We used genome-wide association study (GWAS) summary statistics of 5 typical inflammation markers, 41 inflammatory cytokines, and 731 immune cell signatures, accessed from the public GWAS Catalog. The primary method employed for MR analysis was Inverse Variance Weighted (IVW). To confirm consistency across results, four supplementary MR methods were also conducted: MR-Egger, Weighted Median, Weighted Mode, and Simple Mode. To assess pleiotropy, we used the MR-Egger regression intercept test and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. Cochrane's Q statistic was applied to evaluate heterogeneity. Additionally, the stability of the MR findings was verified through the leave-one-out sensitivity analysis. RESULTS: This study revealed that interleukin-7 (IL-7) and stem cell growth factor beta (SCGF-ß) were possibly associated with the risk of IgAN according to the IVW approach, with estimated odds ratios (OR) of 1.059 (95 % confidence interval [CI] 1.015 to 1.104, P = 0.008) and 1.043 (95 % CI 1.002 to 1.085, P = 0.037). Five immune traits were identified that might be linked to IgAN risk, each with P-values below 0.01, including natural killer T %T cell (OR = 1.058, 95 % CI: 1.020 to 1.097, P = 0.002), natural killer T %lymphocyte (OR = 1.055, 95 % CI: 1.016 to 1.096, P = 0.006), CD25++ CD8+ T cell %T cell (OR = 1.057, 95 % CI: 1.016 to 1.099, P = 0.006), CD3 on effector memory CD4+ T cell (OR = 1.045, 95 % CI: 1.019 to 1.071, P = 0.001), and CD3 on CD28+ CD45RA+ CD8+ T cell (OR = 1.042, 95 % CI: 1.016 to 1.068, P = 0.001). CD4 on central memory CD4+ T cell might be a protective factor for IgAN (OR = 0.922, 95 % CI: 0.875 to 0.971, P = 0.002). Moreover, IgAN may be implicated in a high risk of elevated granulocyte colony-stimulating factor (G-CSF) (OR = 1.114, 95 % CI 1.002 to 1.239, P = 0.046). CONCLUSION: Our study revealed exposures among typical inflammation markers, inflammatory cytokines, and immune cell signatures that may potentially linked to IgAN risk by MR analysis. This insight may advance our understanding of the etiology of IgAN and support the development of targeted therapeutic strategies.

The Role of Peripheral Inflammatory Markers and Coagulation Factors in Patients with Central Nervous System (CNS) Immune Disease and Glioma.

OBJECTIVE: Gliomas are associated with high rates of disability and mortality, and currently, there is a lack of specific and sensitive biomarkers for diagnosis. The ideal biomarkers should be detected early through noninvasive methods. Our research aims to develop a rapid, convenient, noninvasive diagnostic method for gliomas, as well as for grading and differentiation. METHOD: We retrospectively collected data from patients who underwent surgery for glioma, trigeminal neuralgia/hemifacial spasmschwannoma, and those diagnosed with multiple sclerosis at our institution from January 2018 to December 2020. Inflammatory markers and coagulation factor levels were collected on admission, and neutrophil count (NLR), (WBC count minus neutrophil count) / lymphocyte count, platelet count / lymphocyte count, lymphocyte count / monocyte count, and albumin count [g/L] + total lymphocyte count × 5 were calculated for patients. Analyze the significance of biomarkers in the diagnosis and grading of gliomas, the diagnosis of MS, and the differential diagnosis of them. RESULTS: We evaluated 155 healthy individuals, 64 trigeminal neuralgia/hemifacial spasm patients, 47 MS patients, 316 schwannoma patients, and 814 with glioma patients. Compared with healthy controls and MS group, the preoperative levels of NLR, (WBC count minus neutrophil count) / lymphocyte count, D-dimer, Fibrinogen, Antithrobin, and Factor VIII of glioma patients were significantly higher in glioma patients and positively correlated with the grade of glioma. Conversely, 0020 lymphocyte count / Monocyte count and albumin count [g/L] + total lymphocyte count × 5 were significantly lower and negatively correlated with glioma grading. ROC curves confirmed that for the diagnosis of glioma, NLR showed a maximum area under the curve value of 0.8616 (0.8322-0.8910), followed by D-dimer and Antithrombin, with area under the curve values of 0.8205 (0.7601-0.8809) and 0.8455 (0.8153-0.8758), respectively. NLR and d-dimer also showed great sensitivity in the diagnosis of MS and differential diagnosis with gliomas. CONCLUSIONS: Our study demonstrated that multiple inflammatory markers and coagulation factors could be utilized as biomarkers for the glioma diagnosis, grading, and differential diagnosis of MS. Furthermore, the combination of these markers exhibited high sensitivity and specificity.

Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation.

CONTEXT: Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and iron status. Vitamin D supplementation may reduce inflammation. OBJECTIVE AND METHODS: Older adults with early CKD (estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73 m2; CKDG3a/b; n = 35) or normal renal function (eGFR >90 ml/min/1.73 m2; CKDG1; n = 35) received 12,000, 24,000 or 48,000 IU D3/month for 1 year. Markers of the renal-bone axis, inflammation and iron status were investigated pre- and post-supplementation. Predictors of c-terminal and intact FGF23 (cFGF23; iFGF23) were identified by univariate and multivariate regression. RESULTS: Pre-supplementation, comparing CKDG3a/b to CKDG1, plasma cFGF23, iFGF23, PTH, sclerostin and TNFα were significantly higher and Klotho, 1,25-dihydroxyvitamin D and iron were lower. Post-supplementation, only cFGF23, 25(OH)D and IL6 differed between groups. The response to supplementation differed between eGFR groups. Only in the CKDG1 group, phosphate decreased, cFGF23, iFGF23 and procollagen type I N-propeptide increased. In the CKDG3a/b group, TNFα significantly decreased, and iron increased. Plasma 25(OH)D and IL10 increased, and carboxy-terminal collagen crosslinks decreased in both groups. In univariate models cFGF23 and iFGF23 were predicted by eGFR and regulators of calcium and phosphate metabolism at both time points; IL6 predicted cFGF23 (post-supplementation) and iFGF23 (pre-supplementation) in univariate models. Hepcidin predicted post-supplementation cFGF23 in multivariate models with eGFR. CONCLUSION: Alterations in regulators of the renal-bone axis, inflammation and iron status were found in early CKD. The response to vitamin D3 supplementation differed between eGFR groups. Plasma IL6 predicted both cFGF23 and iFGF23 and hepcidin predicted cFGF23.

Platelet-lymphocyte ratio as a predictor of lymph node metastasis in small bowel cancer.

The purpose of this research was to investigate the potential predictive value of preoperative systemic inflammatory indexes in identifying lymph node metastasis among patients diagnosed with small bowel cancer. A retrospective analysis of clinical data was conducted on small bowel cancer patients who underwent surgical treatment at the gastrointestinal surgery department of our hospital between January 2010 and June 2021. Patients were divided into groups based on the presence or absence of lymph node metastasis as confirmed by postoperative pathological results. The study compared the differences in preoperative inflammatory indexes and clinical data between the two groups using single factor analysis and multifactorial Logistic regression analysis. Furthermore, a nomogram model for predicting lymph node metastasis in colorectal cancer was constructed using R software and internally validated. The study sample consisted of 140 small bowel cancer patients,postoperative pathology confirmed lymph node metastasis in 72 cases. Univariate analysis results indicated associations between preoperative inflammatory indexes and clinical data with lymph node metastasis in small bowel cancer. Multifactorial logistic regression analysis revealed that gender, PLR, number of lymph node dissection, and lymphovascular invasion independently influenced lymph node metastasis in small bowel cancer patients. The developed nomogram model demonstrated a C-index of 0.855 (95% CI 0.792-0.917), with a calibrated prediction curve closely resembling the ideal curve. An elevated PLR is an independent risk factor for LNM in patients with small bowel cancer.

Relationship between Prognostic Nutritional Index and Amputation in Patients with Diabetic Foot Ulcer.

The prognostic nutritional index (PNI) is a new marker used to assess a patient's nutritional and immune status. It is calculated using serum albumin levels and total lymphocyte count. The aim of this study was to investigate the relationship between PNI and amputation in patients with diabetic foot ulcer (DFU). Patients with DFU were enrolled in this retrospective study. In our study, a total of 386 patient data, of 110 (28.5%) amputated and 276 (71.5%) non-amputated patients, were statistically analyzed. PNI values were significantly lower in the amputated patient group than in the non-amputee patient group (p < 0.001). According to the ROC analysis results, PNI was significant in the prediction of amputation at an excellent level (AUC = 0.937 (0.911-0.963), p < 0.001). The optimal cut-off point for PNI was found to be 39,005. There was classification success for this cut-off point: sensitivity was calculated as 82.7% (74.1-89) and specificity as 93.1% (89.3-95.7). In the multivariate model, the odds ratio (OR) (95% CI) was calculated as 81.8 (38.5-173.7) for PNI. The PNI was associated with an increase in amputation rate in patients with DFU. By using PNI, patients can be directed to advanced centers and have access to early and appropriate interventions.

Association between inflammation-based prognostic markers and mortality after hip replacement.

We aimed to evaluate the association between inflammation-based prognostic markers and mortality after hip replacement. From March 2010 to June 2020, we identified 5,369 consecutive adult patients undergoing hip replacement with C-reactive protein (CRP), albumin, and complete blood count measured within six months before surgery. Receiver operating characteristic (ROC) curves were generated to evaluate predictabilities and estimate thresholds of CRP-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). Patients were divided according to threshold, and mortality risk was compared. The primary outcome was one-year mortality, and overall mortality was also analyzed. One-year mortality was 2.9%. Receiver operating characteristics analysis revealed areas under the curve of 0.838, 0.832, 0.701, and 0.732 for CAR, NLR, PLR, and modified Glasgow Prognostic Score, respectively. The estimated thresholds were 2.10, 3.16, and 11.77 for CAR, NLR, and PLR, respectively. According to the estimated threshold, high CAR and NLR were associated with higher one-year mortality after adjustment (1.0% vs. 11.7%; HR = 2.16; 95% CI 1.32-3.52; p = 0.002 for CAR and 0.8% vs. 9.6%; HR = 2.05; 95% CI 1.24-3.39; p = 0.01 for NLR), but PLR did not show a significant mortality increase (1.4% vs. 7.4%; HR = 1.12; 95% CI 0.77-1.63; p = 0.57). Our study demonstrated associations of preoperative levels of CAR and NLR with postoperative mortality in patients undergoing hip replacement. Our findings may be helpful in predicting mortality in patients undergoing hip replacement.

Intestinal inflammation marker calprotectin regulates epithelial intestinal zinc metabolism and proliferation in mouse jejunal organoids.

Calprotectin (CP), a heterodimer of S100A8 and S100A9, is expressed by neutrophils and a number of innate immune cells and is used widely as a marker of inflammation, particularly intestinal inflammation. CP is a ligand for toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE). In addition, CP can act as a microbial modulatory agent via a mechanism termed nutritional immunity, depending on metal binding, most notably Zn2+. The effects on the intestinal epithelium are largely unknown. In this study we aimed to characterize the effect of calprotectin on mouse jejunal organoids as a model epithelium, focusing on Zn2+ metabolism and cell proliferation. CP addition upregulated the expression of the Zn2+ absorptive transporter Slc39a4 and of methallothionein Mt1 in a Zn2+-sensitive manner, while downregulating the expression of the Zn2+ exporter Slc30a2 and of methallothionein 2 (Mt2). These effects were greatly attenuated with a CP variant lacking the metal binding capacity. Globally, these observations indicate adaptation to low Zn2+ levels. CP had antiproliferative effects and reduced the expression of proliferative and stemness genes in jejunal organoids, effects that were largely independent of Zn2+ chelation. In addition, CP induced apoptosis modestly and modulated antimicrobial gene expression. CP had no effect on epithelial differentiation. Overall, CP exerts modulatory effects in murine jejunal organoids that are in part related to Zn2+ sequestration and partially reproduced in vivo, supporting the validity of mouse jejunal organoids as a model for mouse epithelium.

Elevated oxidative stress biomarkers in adults with segmented sleep patterns.

STUDY OBJECTIVES: We investigated the association between different sleep patterns and inflammatory and oxidative stress biomarkers in adults. METHODS: A total of 321 consented adults who fulfilled the inclusion criteria were recruited in this cross-sectional study. The inclusion criteria were mainly based on apparently healthy adults aged 18-59 years. To identify sleep patterns, participants were requested to wear the actigraph for 1 week for 24 hours a day. Fasting blood was collected from each participant at day 8. The blood serum was analyzed for inflammatory and oxidative stress biomarkers. Sleep patterns were defined as monophasic (1 episode of night sleep) biphasic (2 episodes of sleep; night and aternoon siesta), and polyphasic sleep pattern (3 or more sleep episodes). RESULTS: There was no correlation between night sleep duration, total sleep in 24 hours, and napping among inflammatory and oxidative stress biomarkers: high-sensitivity C-reactive protein, malondialdehyde, total glutathione, and basal oxidizability status. Actigraphy reports showed 3 sleep patterns in this cohort, monophasic (24.3%), biphasic-napping (45.2%) and polyphasic (30.5%). Individuals with segmented sleep patterns were significantly associated with oxidative stress biomarkers. A polyphasic sleep pattern was significantly associated with higher basal oxidizability status (P = .023), whereas a biphasic sleep pattern showed higher malondialdehyde (P = .036) as compared to a monophasic sleep pattern. Total glutathione was significantly higher in monophasic sleepers (P = .046). There was no difference in serum high-sensitivity C-reactive protein among all sleep patterns. CONCLUSIONS: Segmented sleep in polyphasic and biphasic sleep patterns is associated with higher serum malondialdehyde and basal oxidizability status in particular. Further studies are recommended on the cardiometabolic impact of oxidative stress biomarkers in individuals with segmented sleep. CITATION: Al Lawati I, Zadjali F, Al-Abri MA. Elevated oxidative stress biomarkers in adults with segmented sleep patterns. J Clin Sleep Med. 2024;20(6):959-966.

Eosinophilic bronchiectasis increases length and cost of hospitalization: a retrospective analysis in a hospital of southern China from 2012 to 2020.

BACKGROUND: The concept of eosinophilic bronchiectasis has received clinical attention recently, but the association between blood eosinophil count (BEC) and hospital characteristics has rarely been reported yet. We aim to investigate the clinical impact of BEC on patients with acute bronchiectasis exacerbation. METHODS: A total of 1332 adult patients diagnosed with acute exacerbation of bronchiectasis from January 2012 to December 2020 were included in this retrospective study. A propensity-matched analysis was performed by matching age, sex and comorbidities in patients with high eosinophil count (≥ 300 cell/µL) and low eosinophil count (< 300 cell/µL). Clinical characteristics, length of hospital stay (LOS), hospitalization cost and inflammatory markers were compared between the two groups. RESULTS: Eosinophilic bronchiectasis occurred in approximately 11.7% of all patients. 156 propensity score-matched pairs were identified with and without high eosinophil count. Eosinophilic bronchiectasis presented with a longer LOS [9.0 (6.0-12.5) vs. 5.0 (4.0-6.0) days, p < 0.0001] and more hospitalization cost [15,011(9,753-27,404) vs. 9,109(6,402-12,287) RMB, p < 0.0001] compared to those in non-eosinophilic bronchiectasis. The median white blood cell (WBC), lymphocyte, platelet (PLT) and C-reactive protein (CRP) levels in eosinophilic bronchiectasis were significantly increased. Multivariate logistic regression analysis confirmed that the high levels of eosinophil count (OR = 13.95, p < 0.0001), worse FEV1% predicted (OR = 7.80, p = 0.0003) and PLT (OR = 1.01, p = 0.035) were independent prognostic factors for length of hospital (LOS) greater than 7 days. CONCLUSION: Eosinophilic bronchiectasis patients had longer length of hospital stay and more hospitalization cost compared to those in non-eosinophilic bronchiectasis group, which might be associated with the stronger inflammatory reaction.

Coagulation and Inflammation in COVID-19: Reciprocal Relationship between Inflammatory and Coagulation Markers.

The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), formerly known as 2019-nCoV. Numerous cellular and biochemical issues arise after COVID-19 infection. The severe inflammation that is caused by a number of cytokines appears to be one of the key hallmarks of COVID-19. Additionally, people with severe COVID-19 have coagulopathy and fulminant thrombotic events. We briefly reviewed the COVID-19 disease at the beginning of this paper. The inflammation and coagulation markers and their alterations in COVID-19 illness are briefly discussed in the parts that follow. Next, we talked about NETosis, which is a crucial relationship between coagulation and inflammation. In the end, we mentioned the two-way relationship between inflammation and coagulation, as well as the factors involved in it. We suggest that inflammation and coagulation are integrated systems in COVID-19 that act on each other in such a way that not only inflammation can activate coagulation but also coagulation can activate inflammation.

Healthy lifestyles, systemic inflammation and breast cancer risk: a mediation analysis.

BACKGROUND: Despite the known association between healthy lifestyles and reduced risk of breast cancer, it remains unclear whether systemic inflammation, as a consequence of unhealthy lifestyles, may mediate the association. METHODS: A cohort study of 259,435 female participants in the UK Biobank was conducted to estimate hazard ratio (HR) for breast cancer according to 9 inflammation markers using Cox regression models. We further estimated the percentage of total association between healthy lifestyle index (HLI) and breast cancer that is mediated by these inflammation markers. RESULTS: During 2,738,705 person-years of follow-up, 8,889 cases of breast cancer were diagnosed among 259,435 women in the UK Biobank cohort. Higher level of C-reactive protein (CRP), systemic immune-inflammation index (SII), CRP-to-albumin Ratio (CAR), CRP-to-lymphocyte Ratio (CLR), monocyte-to-HDL-c ratio (MHR), and neutrophil-to-HDL-c ratio (NHR) were associated with increased breast cancer risk, while a higher lymphocyte-to-monocyte ratio (LMR) was associated with a lower risk. The inverse association between HLI and breast cancer was weakly mediated by CRP (8.5%), SII (1.71%), CAR (8.66%), CLR (6.91%), MHR (6.27%), and NHR (7.33%). When considering individual lifestyle factors, CRP and CAR each mediated 16.58% and 17.20%, respectively, of the associations between diet score and breast cancer risk, while the proportion mediated for physical activity and breast cancer were 12.13% and 11.48%, respectively. Furthermore, MHR was found to mediate 13.84% and 12.01% of the associations between BMI, waist circumference, and breast cancer. CONCLUSION: The association of HLI and breast cancer is weakly mediated by the level of inflammation, particularly by CRP and CAR. Systemic inflammatory status may be an intermediate in the biological pathway of breast cancer development.

5+1-Heterocyclization as preparative approach for carboxy-containing triazolo[1,5-c]quinazolines with anti-inflammatory activity.

Present article is devoted to the purposeful search of novel anti-inflammatory agents among carboxyl-containing partially hydrogenated [1,2,4]triazolo[1,5-с]quinazolines and products of their tandem cyclization. It has been shown that target compound's could be obtained via interaction between [2-(3-R-1H-1,2,4-triazol-5-yl)phenyl]amines and oxo-containing carboxylic acids and their esters of various structure. The structures of synthesized compounds were verified by appropriate methods, the features of NMR-spectra patterns were discussed as well. The low predicted toxicity of obtained compounds has been estimated using in silico methods. In vivo study on the model of acute aseptic inflammation (carrageenan test) have been revealed that synthesized compounds expose anti-inflammatory activity in the range of 0.94-52.66%. 4-(2-(Ethoxycarbonyl)-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolin-5-yl)benzoic acid has been identified as most active compound. Additionally, the effects of some (2-R-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazolin-5-yl)benzoic acids (compounds 3) on the levels of key inflammatory markers have been estimated. It has been shown that studied compounds decrease the level of neutrophils, COX-2, nitrotyrosine, IL-1b, C-reactive protein and increase level of eNOS. 4-(2-(Ethoxycarbonyl)-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolin-5-yl)benzoic acid (3.2) has been identified as compound with most expressed anti-inflammatory activity and significant effect on the levels of marker of inflammatory processes. Molecular docking study towards СОХ-1 and СОХ-2 has been conducted to substantiate possible mechanism of obtained compounds anti-inflammatory activity. It has been found that fixation of 4-(2-(ethoxycarbonyl)-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolin-5-yl)benzoic acid (3.2) molecule in active site of enzyme is outstandingly similar to the reference ligands. The essential value of carboxylic group for presence of anti-inflammatory activity has been estimated as result of SAR-analysis. It has been found that studied class of compounds is perspective for further structural modification aimed to the creation of novel anti-inflammatory agents.

Relationships between inflammation markers and the risk of hypertension in primary Sjögren's syndrome: A retrospective cohort study.

OBJECTIVES: The association of inflammation markers with hypertension (HTN) in primary Sjögren's syndrome (pSS) remains controversial. We aimed to investigate whether inflammation markers are at increased risk of developing HTN in pSS patients. METHODS: A retrospective cohort study included pSS patients (n = 380) between May 2011 and May 2020 from the Third People's Hospital of Chengdu. Multivariable Cox regression analyses were used to estimate hazard ratios (HRs) of the potential inflammation markers for pSS-HTN. Subsequently, the dose-response relationships were also used. RESULTS: Out of 380 pSS patients, 171 (45%) developed HTN, and the median follow-up period was 4.16 years. Univariable Cox regression analysis showed that the erythrocyte sedimentation rate (ESR) and neutrophils were significantly associated with the incident HTN (P < 0.05). After adjustment for covariates, this association between ESR (adjusted HR 1.017, 95%CI: 1.005-1.027, P = .003), neutrophils (adjusted HR 1.356, 95%CI: 1.113-1.653, P = .003), and HTN remained significant. The dose-effect relationship was also found between ESR, neutrophils, and HTN (P = .001). CONCLUSIONS: Inflammation markers may play an important role in the incident HTN in pSS.

The potential role of systemic inflammatory markers in predicting recurrence in early-stage cervical cancer.

INTRODUCTION: The influence of systemic inflammatory markers on early-stage cervical cancer (ECC) patients is contradictory. No previous study analyzed whether these markers may be suggestive of recurrence. The aim of this study was to assess whether the inflammatory markers level of patients with recurrence during surveillance was different from those of patients without recurrence representing a risk factor for recurrence. METHODS: Retrospective, single-center, observational study. Patients with 2009 FIGO EEC surgically treated between 2012 and 2019 were included. Baseline inflammatory markers were evaluated on the results of the complete blood count (CBC) and coagulation tests. Inflammatory markers of relapsed patients were evaluated on the last CBC performed before the relapse diagnosis. Inflammatory markers of patients with no recurrence were evaluated on the available CBC taken at the same median follow-up time as the one from relapsed patients. RESULTS: 174 patients were included. Baseline Systemic immune inflammation index (SII) > 663 and Systemic inflammation response index (SIRI) > 0.98 were associated with significant risk of recurrence. SII>663 and Neutrophil to lymphocyte ratio (NLR) > 2.41 were associated with increased risk of death. Significant changes between relapsed (n = 23) and non-relapsed (n = 151) patients in median values of SII (615 versus 490, p-value = 0.001), SIRI (0.74 versus 1.05, p-value = 0.005), NRL (2.95 versus 2.15, p-value = 0.0035), and MLR (0.26 versus 0.22 p-value = 0.020), showed that different levels of inflammatory markers could help identifying recurrent disease during surveillance. CONCLUSION: Baseline SII>663 and SIRI>0.98 were associated with increased risk of recurrence. Higher median values of SII, SIRI, NLR and MLR in relapsed patients highlight their potential association with recurrence.

Microbiological Profiles and Inflammatory Biomarkers of Bacteremia in Children in a Teaching Hospital in Kuwait: An 8-Year Retrospective Study.

OBJECTIVES: The objectives of this study were to determine the bacterial profiles and prevalence of antibiotic resistance patterns of bacteria causing bacteremia in febrile children and to compare levels of inflammatory markers between children with and without bacteremia in Kuwait from 2015 to 2022. MATERIALS AND METHODS: Isolates from all episodes of significant bacteremia (n = 96) during the study period were recorded and evaluated. Microorganisms were identified using standard microbiological methods. Antimicrobial susceptibility testing was carried out using the VITEK2 system and Etest method. Extended-spectrum ß-lactamase (ESBL) production by Enterobacterales was detected by the double-disk diffusion method and VITEK2 system. Patient age, gender, and inflammatory markers were collected at admission and compared between patients with and without bacteremia. RESULTS: A majority of the patients were infants (37, 40%) and newborns (13, 14%). The main ports of entry were the lower respiratory tract, the genitourinary tract, and the gastrointestinal tract. Streptococcus pneumoniae was the most common pathogen (16, 16.7%) followed by Escherichia coli (12, 12.5%), Staphylococcus aureus (10, 10.4%), and Streptococcus agalactiae (9, 9.4%). High rates of resistance to ampicillin, cefuroxime, ciprofloxacin, and trimethoprim-sulfamethoxazole were observed among the Enterobacterales. The prevalence of ESBL-producing E. coli and K. pneumoniae were 45% and 29%, respectively. The prevalence of methicillin-resistant S. aureus was 30%. Patients with bacteremia had significantly higher white blood cell (WBC) counts, absolute neutrophil count (ANC), C-reactive protein (CRP), and neutrophil-lymphocyte ratio (NLR). CONCLUSION: Continuous surveillance of the prevalence and antimicrobial susceptibility patterns of blood isolates is imperative for the formulation of antibiotic policy. WBC, ANC, CRP, and NLR could be valuable indicators of bacteremia in febrile children.

The association between systemic inflammation markers and the prevalence of hypertension.

BACKGROUND: We conducted a large-scale epidemiological analysis to investigate the associations between systemic inflammation markers and hypertension prevalence. Our aim is to identify potential biomarkers for early detection of hypertension. METHODS: A cross-sectional study with 119664 individuals from the National Health and Nutrition Examination Survey was performed. We investigated the associations between three systemic inflammation markers, namely the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), and the prevalence of hypertension. RESULTS: The prevalence rates of hypertension gradually increased with increasing logSII, logSIRI, and logAISI quartiles. In continuous analyses, each unit increase in logSII, logSIRI, and logAISI was associated with a 20.3%, 20.1%, and 23.7% increased risk of hypertension. Compared to those in the lowest quartiles, the hypertension risks for subjects in the highest logSII, logSIRI, and logAISI quartiles were 1.114-fold,1.143-fold, and 1.186-fold. The restricted cubic splines (RCS) analysis revealed a non-linear relationship between the elevation of systemic inflammation markers and hypertension prevalence. Specifically, a per standard deviation increase in any of these variables is associated with a respective 9%, 16%, and 11% increase in hypertension prevalence. CONCLUSION: Our cross-sectional study reveals significant positive correlations between SII, SIRI, and AISI with the prevalence of hypertension.