Association of two novel systemic inflammatory biomarkers and frailty based on NHANES 2007-2018.

Background: Frailty is a significant concern in the field of public health. However, currently, there is a lack of widely recognized and reliable biological markers for frailty. This study aims to investigate the association between systemic inflammatory biomarkers and frailty in the older adult population in the United States. Methods: This study employed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018 and conducted a rigorous cross-sectional analysis. We constructed weighted logistic regression models to explore the correlation between the Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and frailty in the population aged 40 to 80 years. Using restricted cubic spline (RCS), we successfully visualized the relationship between SII, SIRI, and frailty. Finally, we presented stratified analyses and interaction tests of covariates in a forest plot. Results: This study involved 11,234 participants, 45.95% male and 54.05% female, with an average age of 64.75 ± 0.13 years. After adjusting for relevant covariates, the weighted logistic regression model indicated an odds ratio (OR) and 95% confidence interval(CI) for the correlation between frailty and the natural logarithm (ln) transformed lnSII and lnSIRI as 1.38 (1.24-1.54) and 1.69 (1.53-1.88), respectively. Subsequently, we assessed different levels of lnSII and lnSIRI, finding consistent results. In the lnSII group model, the likelihood of frailty significantly increased in the fourth quartile (OR = 1.82, 95% CI: 1.55-2.12) compared to the second quartile. In the lnSIRI group model, the likelihood of frailty significantly increased in the third quartile (OR = 1.30, 95% CI: 1.10-1.53) and fourth quartile (OR = 2.29, 95% CI: 1.95-2.70) compared to the second quartile. The interaction results indicate that age and income-to-poverty ratio influence the association between lnSIRI and frailty. RCS demonstrated a nonlinear relationship between lnSII, lnSIRI, and frailty. Conclusion: The results of this cross-sectional study indicate a positive correlation between systemic inflammatory biomarkers (SII, SIRI) and frailty.

Comparative Impact of an Optimized PK/PD Target Attainment of Piperacillin-Tazobactam vs. Meropenem on the Trend over Time of SOFA Score and Inflammatory Biomarkers in Critically Ill Patients Receiving Continuous Infusion Monotherapy for Treating Documented Gram-Negative BSIs and/or VAP.

(1) Background: The advantage of using carbapenems over beta-lactam/beta-lactamase inhibitor combinations in critically ill septic patients still remains a debated issue. We aimed to assess the comparative impact of an optimized pharmacokinetic/pharmacodynamic (PK/PD) target attainment of piperacillin-tazobactam vs. meropenem on the trend over time of both Sequential Organ Failure Assessment (SOFA) score and inflammatory biomarkers in critically ill patients receiving continuous infusion (CI) monotherapy with piperacillin-tazobactam or meropenem for treating documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP). (2) Methods: We performed a retrospective observational study comparing critically ill patients receiving targeted treatment with CI meropenem monotherapy for documented Gram-negative BSIs or VAP with a historical cohort of critical patients receiving CI piperacillin-tazobactam monotherapy. Patients included in the two groups were admitted to the general and post-transplant intensive care unit in the period July 2021-September 2023 and fulfilled the same inclusion criteria. The delta values of the SOFA score between the baseline of meropenem or piperacillin-tazobactam treatment and those at 48-h (delta 48-h SOFA score) or at 7-days (delta 7-days SOFA) were selected as primary outcomes. Delta 48-h and 7-days C-reactive protein (CRP) and procalcitonin (PCT), microbiological eradication, resistance occurrence, clinical cure, multi-drug resistant colonization at 90-day, ICU, and 30-day mortality rate were selected as secondary outcomes. Univariate analysis comparing primary and secondary outcomes between critically ill patients receiving CI monotherapy with piperacillin-tazobactam vs. meropenem was carried out. (3) Results: Overall, 32 critically ill patients receiving CI meropenem monotherapy were compared with a historical cohort of 43 cases receiving CI piperacillin-tazobactam monotherapy. No significant differences in terms of demographics and clinical features emerged at baseline between the two groups. Optimal PK/PD target was attained in 83.7% and 100.0% of patients receiving piperacillin-tazobactam and meropenem, respectively. No significant differences were observed between groups in terms of median values of delta 48-h SOFA (0 points vs. 1 point; p = 0.89) and median delta 7-days SOFA (2 points vs. 1 point; p = 0.43). Similarly, no significant differences were found between patients receiving piperacillin-tazobactam vs. meropenem for any of the secondary outcomes. (4) Conclusion: Our findings may support the contention that in critically ill patients with documented Gram-negative BSIs and/or VAP, the decreases in the SOFA score and in the inflammatory biomarkers serum levels achievable with CI piperacillin-tazobactam monotherapy at 48-h and at 7-days may be of similar extent and as effective as to those achievable with CI meropenem monotherapy provided that optimization on real-time by means of a TDM-based expert clinical pharmacological advice program is granted.

Antioxidative and Anti-inflammatory Effects of Plant-derived Hypoglycemic Medicines: An In vivo/In vitro Systematic Review.

BACKGROUND: The activation of oxidative stress and inflammatory conditions has been associated with acceleration in diabetes (DM) onset and complications. Despite various anti-DM medications, there is a growing trend to discover inexpensive and effective treatments with low adverse effects from plants as one of the promising sources for drug development. OBJECTIVE: This study aimed to systematically investigate the simultaneous anti-inflammatory and antioxidant effects of plant-derived hypoglycemic medicines in diabetic experimental models. METHODS: The search terms consisted of "diabetes", "herbal medicine", "antioxidant", "Inflammatory biomarker", and their equivalents among PubMed, Scopus, Web of Science, and Cochrane Library databases up to 17 August 2021. RESULTS: Throughout the search of databases, 201 eligible experimental studies were recorded. The results showed that the most commonly assessed inflammatory and oxidative stress biomarkers were tumor necrosis factor (TNF)-α, interleukin (IL) 6, IL-1ß, IL-10, malondialdehyde (MDA), and nitric oxide (NO). The activity of antioxidant enzymes, including superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were assessed in the present review. Among herbal treatments, Trigonella foenum-graecum L., Centella asiatica (L.) Urb., Vitis vinifera L., and Moringa oleifera Lam. were most commonly used for diabetic complications. Due to the dispersion of the treatments, meta-analysis was not applicable. CONCLUSION: Our findings showed that the application of different plant-derived hypoglycemic treatments in animal models improved diabetes and its complications, as well as modulated concomitant inflammatory and oxidative stress biomarkers. These findings suggest that plant-based antidiabetic medicines and food supplements have the potential to manage diabetes and its complications.

A nomogram model based on the systemic immune-inflammation index to predict the risk of venous thromboembolism in elderly patients after hip fracture: A retrospective cohort study.

Background and objectives: Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and secondary pulmonary embolism (PE), represents a significant complication post-hip fracture in the elderly. It is a prevalent cause of VTE-related complications, prolonged hospitalization, and mortality. This study aimed to investigate the potential of the systemic immune-inflammation index (SII) as a predictive marker for VTE in older patients following hip fracture. Methods: The study was structured as an observational, analytical, retrospective cohort analysis. A total of 346 elderly patients diagnosed with hip fracture were included. We retrospectively collated clinical and laboratory data for these patients. Using the bootstrap method, the patients were divided in a 7:3 ratio into a training cohort (DVT group = 170 patients; no-DVT group = 72 patients) and an internal validation cohort (DVT group = 81 patients; no-DVT group = 23 patients). In the training cohort, relevant indices were initially identified using univariate analysis. Subsequently, least absolute shrinkage and selection operator logistic analysis was employed to determine significant potential independent risk factors (P < 0.05). A dynamic online diagnostic nomogram was developed, with its discriminative ability assessed using the area under the receiver operating characteristic curve (AUC). The nomogram's accuracy was further appraised using calibration plots. The clinical utility of the nomogram was evaluated through decision curve analysis (DCA) and corroborated by internal validation within the training set. Results: SII emerged as the sole independent risk factor identified from the multivariate logistic analysis of the training cohort and was incorporated into the VTE diagnostic nomogram for older patients' post-hip fracture. The nomogram demonstrated AUC values of 0.648 in the training cohort and 0.545 in the internal testing cohort. Calibration curves corroborated the close alignment of the nomogram's predicted outcomes with the ideal curve, indicating consistency between predicted and actual outcomes. The DCA curve suggested that all patients could derive benefit from this model. These findings were also validated in the validation cohort. Conclusion: The systemic immune-inflammation index is a robust predictor of venous thromboembolism in elderly patients following hip fracture, underscoring its potential as a valuable tool in clinical practice.

Gastroprotective Effect of 2,3-Dimethylquinoxaline Against Indomethacin-Induced Gastric Ulcer in Rat.

Background: Gastric ulcers pose a significant health risk due to an imbalance between protective and aggressive factors on the mucous membrane. Nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage affects 25% of users. Quinoxaline compounds, known for their diverse biological properties, have potential applications in cancer therapy and as antimicrobial agents targeting various pathogens. Objective: Our study aimed to investigate the impact of DMQ on gastroprotective mechanisms in an experimental model of indomethacin-induced gastric ulcer. Methods: Thirty male Wistar rats were randomly assigned to five groups. Group 1 served as the control, while Group 2 received a single oral dose of IND (30 mg/kg). Groups 3 and 4 received oral DMQ (30 mg/kg and 60 mg/kg, respectively) for three days, with the final dose administered intragastrically one hour before IND administration. Group 5 received esomeprazole (30 mg/kg) orally for three days, with the final dose given one hour before IND administration. Rats were sacrificed four hours after IND induction. Results: Indomethacin-induced ulcers were associated with epithelial damage and blood streaks on the gastric mucosa. However, DMQ significantly decreased levels of inflammatory biomarkers (TNF-α, IL-6, Cox-2, IFN-γ, and IL-ß1) while increasing gastroprotective mediator prostaglandin E2 (PGE2) and mucin levels. Histopathological analysis revealed a significant reduction in ulcer-induced pathological alterations and upregulation of tumor suppressor genes (NF-κB levels) following DMQ treatment. Rats treated with Indo+DMQ showed a significant decrease in ulcer index compared to the Indo group, with mild injuries observed. Conclusion: DMQ demonstrated promising gastroprotective effects against IND-induced gastric ulcers, as evidenced by alterations in histopathological data and upregulation of gene expression.

Prediction of pCR based on clinical-radiomic model in patients with locally advanced ESCC treated with neoadjuvant immunotherapy plus chemoradiotherapy.

Background: The primary objective of this research is to devise a model to predict the pathologic complete response in esophageal squamous cell carcinoma (ESCC) patients undergoing neoadjuvant immunotherapy combined with chemoradiotherapy (nICRT). Methods: We retrospectively analyzed data from 60 ESCC patients who received nICRT between 2019 and 2023. These patients were divided into two cohorts: pCR-group (N = 28) and non-pCR group (N = 32). Radiomic features, discerned from the primary tumor region across plain, arterial, and venous phases of CT, and pertinent laboratory data were documented at two intervals: pre-treatment and preoperation. Concurrently, related clinical data was amassed. Feature selection was facilitated using the Extreme Gradient Boosting (XGBoost) algorithm, with model validation conducted via fivefold cross-validation. The model's discriminating capability was evaluated using the area under the receiver operating characteristic curve (AUC). Additionally, the clinical applicability of the clinical-radiomic model was appraised through decision curve analysis (DCA). Results: The clinical-radiomic model incorporated seven significant markers: postHALP, ΔHB, post-ALB, firstorder_Skewness, GLCM_DifferenceAverage, GLCM_JointEntropy, GLDM_DependenceEntropy, and NGTDM_Complexity, to predict pCR. The XGBoost algorithm rendered an accuracy of 0.87 and an AUC of 0.84. Notably, the joint omics approach superseded the performance of solely radiomic or clinical model. The DCA further cemented the robust clinical utility of our clinical-radiomic model. Conclusion: This study successfully formulated and validated a union omics methodology for anticipating the therapeutic outcomes of nICRT followed by radical surgical resection. Such insights are invaluable for clinicians in identifying potential nICRT responders among ESCC patients and tailoring optimal individualized treatment plans.

Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly recognized for their role in reducing the risk and improving the prognosis of heart failure (HF). However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in mitigating the risk of HF. METHODS: A two-sample, two-step Mendelian Randomization (MR) approach was employed to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship. MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium. The Genome-wide association study (GWAS) data for 92 inflammatory biomarkers were obtained from two datasets, which included 14,824 and 575,531 individuals of European ancestry, respectively. GWAS data for HF was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) and 95% confidence interval (CI) for HF were calculated per 1 unit change of HbA1c. RESULTS: Genetically predicted SGLT-2 inhibition was associated with a reduced risk of HF (OR 0.42 [95% CI 0.30-0.59], P < 0.0001). Of the 92 inflammatory biomarkers studied, two inflammatory biomarkers (C-X-C motif chemokine ligand 10 [CXCL10] and leukemia inhibitory factor) were associated with both SGLT-2 inhibition and HF. Multivariable MR analysis revealed that CXCL10 was the primary inflammatory cytokine related to HF (MIP = 0.861, MACE = 0.224, FDR-adjusted P = 0.0844). The effect of SGLT-2 inhibition on HF was mediated by CXCL10 by 17.85% of the total effect (95% CI [3.03%-32.68%], P = 0.0183). CONCLUSIONS: This study provides genetic evidence supporting the anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing the risk of HF. CXCL10 emerged as a potential mediator, offering a novel intervention pathway for HF treatment.

The association between inflammatory biomarkers and low back disorder: a systematic review and meta-analysis.

INTRODUCTION: Low back disorder (LBD) is a major cause of disability worldwide. Inflammation results in proliferation of cytokines or consequent degradation products (collectively known as inflammatory biomarkers) that activate pain pathways which can result in non-specific LBD. This systematic review and meta-analysis aim to evaluate the relationship between inflammatory biomarkers and clinical outcomes in patients with LBD. METHODS: The PRISMA guideline was followed for the systematic reivew. Three online databases were searched. Four RCTs and sixteen observational studies with 1142 LBD patients were analysed. The primary outcomes were back and leg pain scores, back-specific disability scores and expression of inflammatory biomarkers. Standardized mean difference (SMD) and their 95% confidence intervals (CI) were evaluated. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to summarize the strength of evidence. RESULTS: Four RCTs and sixteen observational studies were included in the analysis of 1142 patients with LBD. There was a statistically significant reduction in back pain score and IL-1 beta and increase in the expression of CTX-1 and IL-10 levels post treatment. There was a significant relationship between increase in the expression of MCP- and reduction in the expression of hsCRP with increase in back pain. Significant relationship was also observed between increase in the expression of MCP-1 and reduction in the expression of IL-6 with increase in leg pain. Increase in the expression of IL-8 and reduction in the expression of hsCRP was also associated with increased disability score. CONCLUSION: Inflammatory biomarkers play a significant role in the pathogenesis of LBD. CTX-1, IL-10 and IL-1 beta may be responsible for the decrease in back pain scores post treatment. There is a relationship between MCP-1, IL-6, IL-8 and hsCRP with clinical and functional assessments for LBD. Further studies will improve understanding of the pathogenesis of LBD and aid in targeted management strategies.

Racial Differences in Vaginal Fluid Metabolites and Association with Systemic Inflammation Markers among Ovarian Cancer Patients: A Pilot Study.

The vaginal microbiome differs by race and contributes to inflammation by directly producing or consuming metabolites or by indirectly inducing host immune response, but its potential contributions to ovarian cancer (OC) disparities remain unclear. In this exploratory cross-sectional study, we examine whether vaginal fluid metabolites differ by race among patients with OC, if they are associated with systemic inflammation, and if such associations differ by race. Study participants were recruited from the Ovarian Cancer Epidemiology, Healthcare Access, and Disparities Study between March 2021 and September 2022. Our study included 36 study participants with ovarian cancer who provided biospecimens; 20 randomly selected White patients and all 16 eligible Black patients, aged 50-70 years. Acylcarnitines (n = 45 species), sphingomyelins (n = 34), and ceramides (n = 21) were assayed on cervicovaginal fluid, while four cytokines (IL-1ß, IL-10, TNF-α, and IL-6) were assayed on saliva. Seven metabolites showed >2-fold differences, two showed significant differences using the Wilcoxon rank-sum test (p < 0.05; False Discovery Rate > 0.05), and 30 metabolites had coefficients > ±0.1 in a Penalized Discriminant Analysis that achieved two distinct clusters by race. Arachidonoylcarnitine, the carnitine adduct of arachidonic acid, appeared to be consistently different by race. Thirty-eight vaginal fluid metabolites were significantly correlated with systemic inflammation biomarkers, irrespective of race. These findings suggest that vaginal fluid metabolites may differ by race, are linked with systemic inflammation, and hint at a potential role for mitochondrial dysfunction and sphingolipid metabolism in OC disparities. Larger studies are needed to verify these findings and further establish specific biological mechanisms that may link the vaginal microbiome with OC racial disparities.

Impact of 1-Year Supplementation with High-Rich Docosahexaenoic Acid (DHA) on Clinical Variables and Inflammatory Biomarkers in Pediatric Cystic Fibrosis: A Randomized Double-Blind Controlled Trial.

A randomized, double-blind, and placebo-controlled study was conducted to assess the effect of dietary supplementation with high-rich docosahexaenoic acid (DHA) (Tridocosahexanoin-AOX® 70%) at 50 mg/kg/day in pediatric patients with cystic fibrosis (CF) as compared with placebo. The duration of supplementation was 12 months. A total of 22 patients were included, with 11 in the DHA group and 11 in the placebo group. The mean age was 11.7 years. The outcome variables were pulmonary function, exacerbations, sputum cellularity, inflammatory biomarkers in sputum and peripheral blood, and anthropometric variables. In the DHA group, there was a significant increase in FVC (p = 0.004) and FVE1 expressed in liters (p = 0.044) as compared with placebo, and a lower median number of exacerbations (1 vs. 2). Differences in sputum cellularity (predominantly neutrophilic), neutrophilic elastase, and sputum and serum concentrations of resolvin D1 (RvD1), interleukin (IL)-8 (IL-8), and tumor necrosis factor alpha (TNF-α) between the study groups were not found. Significant increases in weight and height were also observed among DHA-supplemented patients. The administration of the study product was safe and well tolerated. In summary, the use of a highly concentrated DHA supplement for 1 year as compared with placebo improved pulmonary function and reduced exacerbations in pediatric CF.

Endotoxin Inflammatory Action on Cells by Dysregulated-Immunological-Barrier-Linked ROS-Apoptosis Mechanisms in Gut-Liver Axis.

Our study highlighted the immune changes by pro-inflammatory biomarkers in the gut-liver-axis-linked ROS-cell death mechanisms in chronic and acute inflammations when gut cells are exposed to endotoxins in patients with hepatic cirrhosis or steatosis. In duodenal tissue samples, gut immune barrier dysfunction was analyzed by pro-inflammatory biomarker expressions, oxidative stress, and cell death by flow cytometry methods. A significant innate and adaptative immune system reaction was observed as result of persistent endotoxin action in gut cells in chronic inflammation tissue samples recovered from hepatic cirrhosis with the A-B child stage. Instead, in patients with C child stage of HC, the endotoxin tolerance was installed in cells, characterized by T lymphocyte silent activation and increased Th1 cytokines expression. Interesting mechanisms of ROS-cell death were observed in chronic and acute inflammation samples when gut cells were exposed to endotoxins and immune changes in the gut-liver axis. Late apoptosis represents the chronic response to injury induction by the gut immune barrier dysfunction, oxidative stress, and liver-dysregulated barrier. Meanwhile, necrosis represents an acute and severe reply to endotoxin action on gut cells when the immune system reacts to pro-inflammatory Th1 and Th2 cytokines releasing, offering protection against PAMPs/DAMPs by monocytes and T lymphocyte activation. Flow cytometric analysis of pro-inflammatory biomarkers linked to oxidative stress-cell death mechanisms shown in our study recommends laboratory techniques in diagnostic fields.

Systemic immune-inflammatory biomarkers (SII, NLR, PLR and LMR) linked to non-alcoholic fatty liver disease risk.

Background: Systemic immune-inflammatory biomarkers including systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have been demonstrated to be associated with the risk and severity of various liver diseases. However, studies on their role and clinical significance in metabolic diseases, especially in nonalcoholic fatty liver disease (NAFLD), are limited and results are inconsistent. Methods: 10821 adults aged 20 years or older were enrolled in this cross-sectional study, sourced from six cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted logistic regression was employed to investigate the correlation between systemic immune-inflammatory biomarkers (SII, NLR, PLR, and LMR) and NAFLD risk. Restricted cubic spline regression models and segmented regression models were used to describe nonlinear relationships and threshold effects. Subgroup and sensitivity analyses were also conducted. Results: After adjusting for all confounding variables, there was a significant positive association observed between ln-transformed SII (OR= 1.46, 95% CI: 1.27-1.69, P <0.001), NLR (OR= 1.25, 95% CI: 1.05-1.49, P =0.015), LMR (OR= 1.39, 95% CI: 1.14-1.69, P = 0.002) with NAFLD. A nonlinear dose-response relationship with an inverted "U"-shaped threshold of 4.64 was observed between ln(PLR) and NAFLD risk. When ln(PLR) was below 4.64, each unit increase in ln(PLR) was associated with a 0.55-fold increase in the risk of NAFLD (OR= 1.55, 95% CI: 1.05-2.31, P <0.05). Conversely, when ln(PLR) exceeded 4.64, each unit increase in ln(PLR) was associated with a 0.40-fold decrease in the risk of NAFLD (OR= 0.60, 95% CI. 0.44-0.81, P <0.05). Conclusion: ln-transformed SII, NLR, and LMR were linearly associated with NAFLD risk. ln(PLR) showed an inverted "U"-shaped nonlinear dose-response relationship with the risk of NAFLD.

Inflammatory synovial biomarkers and state of the tibiofemoral joint in the post-surgical settings: a narrative review.

Background and Objective: Knee surgery attempts to restore the native biomechanics of the knee, improve stability, and decrease the progression of osteoarthritis (OA). However, despite improvements in surgical techniques, tissue degradation and OA are common after knee surgery, occurring in higher rates in surgical knees compared to non-surgical knees. The aim of this study is to analyze previous literature to determine which synovial fluid biomarkers contribute to knee tissue degradation and decrease patient outcomes in the post-surgical setting of the knee. Methods: A narrative review of relevant literature was performed in July 2023. Studies reporting on synovial biomarkers associated with the post-surgical knee were included. Key Content and Findings: The literature reported that proinflammatory synovial biomarkers cause cartilage degradation and turnover which eventually leads to OA. The associated biomarkers are typically present prior to physical symptoms so understanding which one's correlate to OA is important for potential therapeutic treatments in the future. Studying the preoperative, early postoperative, and late postoperative synovial biomarkers will allow physicians to develop an improved understanding of how these biomarkers progress and correlate to knee tissue degradation and OA. This understanding could lead to further developments into potential treatment options. Research into inhibiting or reversing these inflammatory biomarkers to slow the progression of knee tissue degradation has already begun and has reported some promising results but is currently limited in scope. Conclusions: Synovial fluid biomarkers in the post-surgical knee setting may contribute to decreased patient outcomes and the progression of knee tissue degradation. There is no current consensus on which of these biomarkers are the most detrimental or associated with decreased patient outcomes. With an improved understanding of the individual biomarkers, potential personalized therapeutic treatment could be used by physicians in the future to improve patient outcomes after surgery.

Genetic factors associated with age-related macular degeneration modulating plasma inflammatory biomarker levels in patients with AIDS.

INTRODUCTION: Patients with the acquired immunodeficiency syndrome (AIDS) have an increased prevalence and incidence of intermediate-stage age-related macular degeneration (AMD). Several elevated plasma inflammatory biomarkers are associated with increased incidence of intermediate-stage AMD in this population. We evaluated the association between AMD risk alleles and plasma inflammatory biomarker levels in persons with AIDS. MATERIALS AND METHODS: Cryopreserved plasma specimens of 229 non-Hispanic White and 252 non-Hispanic blacks from the Longitudinal Study of the Ocular Complications of AIDS cohort were assayed for plasma levels of soluble tumor necrosis factor receptor (sTNFR) 2, interleukin (IL)-18, C × 3motif chemokine ligand 1 (CX3CL1), C-reactive protein (CRP), and soluble CD14 (sCD14). Genotyping included AMD-associated variants rs10801553 and rs800292 for complement factor H (CFH) rs9332739 and rs547154 for complement factor 2 (C2), rs2230199 for C3, rs2285714 for CFI, and rs3732379 and rs3732378 for C × 3motif chemokine receptor 1 (CX3CR1). RESULTS: In Whites, AMD low-risk CX3CR1 variants (V249I and T280M) were associated with reduced plasma levels of IL-18. In Blacks, AMD low-risk C3 R102G and low-risk CX3CR1 T280M variants were associated with reduced CRP levels. CONCLUSIONS: Genetic variants in AMD-associated immune genes may influence AMD-associated systemic plasma inflammatory biomarker levels in patients with AIDS.

Adiponectin and HbA1c levels among Indian patients with diabetes mellitus.

Adiponectin is closely related to glucose metabolism and newly diagnosed type 2 diabetes mellitus (T2DM), and other kinds of diabetes linked to the risk of T2DM. Therefore, it is of interest to report the correlation between adiponectin levels and glycosylated hemoglobin (HbA1c) as a diagnostic marker of T2DM and healthy control. Total 210 participants were included of IPD & OPD healthy controls with glycosylated hemoglobin levels under 6% were included. Blood samples, collected using sterile clot activator or plain vials, were stored at -20°C. The biomarker score that comprised significant differences in age, gender distribution, and metabolic indicators are seen between the diabetes (n=105) and control (n=105) groups. Increase in both Adiponectin and HbA1c% Mean±SD (6.86±0.23, p<0.0001; 22.71±2.01; p<0.0001) is indicative of deteriorating glycaemic control and an accompanying rise in inflammatory response. Positively correlate adiponectin levels with HbA1c levels (r2=0.398; p<0.0001), suggesting a link between inflammatory response and glucose control. Lower adiponectin levels are statistically associated with diabetes. Diabetes and adiponectin were negatively correlated and positive linear relationship between HbA1c and adiponectin levels. Adiponectin may be a significant factor useful in understanding the pathophysiology; they are likely to be straight forward instruments for predicting future risk of diabetes.

A Dynamic Online Nomogram Based on Gd-EOB-DTPA-Enhanced MRI and Inflammatory Biomarkers for Preoperative Prediction of Pathological Grade and Stratification in Solitary Hepatocellular Carcinoma: A Multicenter Study.

BACKGROUND: Hepatocellular carcinoma (HCC) is an inflammatory cancer. We aimed to explore whether preoperative inflammation biomarkers compared to the gadoxetic acid disodium (Gd-EOB-DTPA) enhanced MRI can add complementary value for predicting HCC pathological grade, and to develop a dynamic nomogram to predict solitary HCC pathological grade. METHODS: 331 patients from the Institution A were divided chronologically into the training cohort (n = 231) and internal validation cohort (n = 100), and recurrence-free survival (RFS) was determined to follow up after surgery. 79 patients from the Institution B served as the external validation cohort. Overall, 410 patients were analyzed as the complete dataset cohort. Least absolute shrinkage and selection operator (LASSO) and multivariate Logistic regression were used to gradually filter features for model construction. The area under the receiver operating characteristic curve (AUC) and decision curve analysis were used to evaluate model's performance. RESULTS: Five models of the inflammation, imaging, inflammation+AFP, inflammation+imaging and nomogram were developed. Adding inflammation to imaging model can improve the AUC in training cohort (from 0.802 to 0.869), internal validation cohort (0.827 to 0.870), external validation cohort (0.740 to 0.802) and complete dataset cohort (0.739 to 0.788), and obtain more net benefit. The nomogram had excellent performance for predicting high-grade HCC in four cohorts (AUCs: 0.882 vs. 0.869 vs. 0.829 vs. 0.806) with a good calibration, and accessed at https://predict-solitaryhccgrade.shinyapps.io/DynNomapp/. Additionally, the nomogram obtained an AUC of 0.863 (95% CI 0.797-0.913) for predicting high-grade HCC in the HCC≤ 3 cm. Kaplan-Meier survival curves demonstrated that the nomogram owned excellent stratification for HCC grade (P < 0.0001). CONCLUSION: This easy-to-use dynamic online nomogram hold promise for use as a noninvasive tool in prediction HCC grade with high accuracy and robustness.

Peripheral inflammatory biomarkers as predictive tools for HyperCKemia risk assessment post-seizures.

BACKGROUND: This study evaluates the potential of inflammatory biomarkers, especially the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), for early detection of hyperCKemia after seizures. Addressing the challenge of delayed hyperCKemia diagnosis, which can escalate to rhabdomyolysis, this research emphasizes the use of these accessible biomarkers. METHODS: Conducted retrospectively, data from October 1, 2022, and October 1, 2023, were extracted from electronic medical records. Following univariate analysis (P-value < 0.05 for selection), Spearman's rank correlation and binary logistics regression were employed to examine the relationship between hyperCKemia and various clinical variables. Receiver operating characteristic curves (ROCs) defined the cut-off values for seizure-related hyperCKemia. RESULTS: Among 98 seizure patients, 31 (31.63 %) developed hyperCKemia. Notable differences in leukocytes, neutrophils, CRP, and NLR levels were observed between hyperCKemia and normal CK groups (P < 0.05). Leukocytes, NLR, and CRP correlated with hyperCKemia, exhibiting odds ratios of 1.24 (95 % CI: 1.11-1.39, P < 0.001), 1.03 (95 % CI: 1.01-1.05, P = 0.001), and 1.22 (95 % CI: 1.09-1.35, P = 0.017). The optimal cut-off values were established as 9.78 × 10^9/L for leukocytes, 32.40 mg/L for CRP, and 7.35 for NLR. CONCLUSION: Elevated levels of leukocytes, CRP, and NLR post-seizure are strong indicators of hyperCKemia risk, with significant implications for enhancing clinical decision-making and patient care strategies.

The Role of Sequentially Monitored Laboratory Values and Inflammatory Biomarkers in Assessing the Severity of COVID-19.

With the onset of the pandemic in 2020, COVID-19 pneumonia has become a common cause for hospitalization and is associated with high mortality rates. Inflammatory biomarkers play a crucial role in understanding and monitoring the progression of various diseases, including COVID-19. The objective of this study was to assess the significance of sequentially monitored standard laboratory tests, including complete blood cell count, D-dimer, fibrinogen, ferritin, albumin, C-reactive protein (CRP), as well as newly calculated inflammatory biomarkers in predicting the severity and prognosis of COVID-19 pneumonia. This single-center retrospective study included 194 patients hospitalized due to COVID-19 pneumonia. Patients were grouped based on the severity of their clinical symptoms, with 134 categorized as severe disease and 60 as mild-moderate disease. The patients' demographic data and laboratory values at hospital admission and on the third day of hospitalization were comparatively evaluated. In the severe illness group, there were more complaints about shortness of breath and a significant drop in the SPO2 value was observed at the time of application (p =0.005 and p<0.001, respectively). The overall mortality rate in all patients was 9% (18/194), and all deaths occurred within the severe disease group. All laboratory parameters, with the exception of platelet count and ferritin levels, were significantly associated and correlated with the severity of the disease during the hospitalization period. Among the biomarkers, there was no significant difference in neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) on the first day, a significant increase was observed on the third day of hospitalization in the severe disease group (p=0.050 vs. 0.003 and p=0.073 vs. 0.020, respectively). No significant difference was observed only in the PNR (platelet/neutrophil ratio) value among the inflammatory biomarkers (p=0.090 vs. p=0.354). In conclusion, the SPO2 level of COVID-19 patients at admission and the subsequent laboratory parameters examined show a significant relationship with the severity of the disease. In addition, simple inflammation biomarkers derived from laboratory values have shown a very significant relationship and correlation in the diagnosis and follow-up of the disease. In both admission and follow-up evaluation, a more significant association was observed with CRP-related biomarkers such as CRP/albumin ratio and CRP/lymphocyte ratio rather than NLR and PLR, which are widely used in the literature, in showing the severity of COVID-19. In patients with pneumonia, the laboratory assessment made on the third day of hospitalization reflects the severity of the disease more clearly than on the first day.

A method of quantitative chemiluminescence immunoassay for the concentration of Growth differentiation factor-15.

Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor (TGF-ß) superfamily, and is expressed and secreted in response to inflammation, oxidative stress and hypoxia. It has been shown in several studies to be a predictor of heart failure. However, the only kits available on the market are ELISA kits, which are costly and error-prone and are not conducive for clinical use. Here, we developed a chemiluminescence kit which optimized the reaction conditions and the reaction time was reduced to 10 min. We further proved that it can be used to measure GDF-15 in serum or plasma accurately and fastly, and provide additional information for the diagnosis of heart failure disease. Methodological comparison and clinical study verified this method is a reliable, economical and highly automated blood test method.•All necessary steps and the reagents needed are provided.•Reliability of the chemiluminescence immunoassay was verified by analyzing serum GDF-15 levels from different groups.•GDF-15 can provide clinicians with reliable prediction and disease assessment of heart failure.

Association between inflammatory biomarkers and mortality in individuals with type 2 diabetes: NHANES 2005-2018.

PURPOSE: This study aimed to examine independent association between inflammatory biomarkers and all-cause mortality as well as cardio-cerebrovascular disease (CCD) mortality among U.S. adults with diabetes. METHODS: A cohort of 6412 U.S. adults aged 20 or older was followed from the start until December 31, 2019. Statistical models such as Cox proportional hazards model (Cox) and Kaplan-Meier (K-M) survival curves were employed to investigate the associations between the inflammatory biomarkers and all-cause mortality and CCD mortality. RESULTS: After adjusting for confounding factors, the highest quartile of inflammatory biomarkers (NLR HR = 1.99; 95 % CI:1.54-2.57, MLR HR = 1.93; 95 % CI:1.46-2.54, SII HR = 1.49; 95 % CI:1.18-1.87, SIRI HR = 2.32; 95 % CI:1.81-2.96, nLPR HR = 2.05; 95 % CI:1.61-2.60, dNLR HR = 1.94; 95 % CI:1.51-2.49, AISI HR = 1.73; 95 % CI:1.4 1-2.12)) were positively associated with all-cause mortality compared to those in the lowest quartile. K-M survival curves indicated that participants with an inflammatory biomarker above a certain threshold had a higher risk of both all-cause mortality and CCD mortality (Log rank P < 0.05). CONCLUSION: Some biomarkers such as NLR, MLR, SII, AISI, SIRI, and dNLR, are significantly associated with all-cause mortality and CCD mortality among U.S. adults with diabetes. The risk of both outcomes increased when the biomarkers surpassed a specific threshold.